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Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine

Francisco Vizoso, Noemi Eiro, Sandra Cid and 2 more

International Journal of Molecular Sciences · 2017 · Review · CC BY

Abstract

Earlier research primarily attributed the effects of mesenchymal stem cell (MSC) therapies to their capacity for local engrafting and differentiating into multiple tissue types. However, recent studies have revealed that implanted cells do not survive for long, and that the benefits of MSC therapy could be due to the vast array of bioactive factors they produce, which play an important role in the regulation of key biologic processes. Secretome derivatives, such as conditioned media or exosomes, may present considerable advantages over cells for manufacturing, storage, handling, product shelf life and their potential as a ready-to-go biologic product. Nevertheless, regulatory requirements for manufacturing and quality control will be necessary to establish the safety and efficacy profile of these products. Among MSCs, human uterine cervical stem cells (hUCESCs) may be a good candidate for obtaining secretome-derived products. hUCESCs are obtained by Pap cervical smear, which is a less invasive and painful method than those used for obtaining other MSCs (for example, from bone marrow or adipose tissue). Moreover, due to easy isolation and a high proliferative rate, it is possible to obtain large amounts of hUCESCs or secretome-derived products for research and clinical use.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 15, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Stem Cells and Regenerative Medicine

1Stem cells are immature tissue precursor cells that are able to self-renew, have the ability to form clonal cell populations, and differentiate into multiple cell lineages. These special properties are particularly attractive for restoring function in multiple tissues. Currently, the broad diversity of stem cells can be divided into three categories: (i) embryonic stem cells derived from early stage embryos; (ii) induced pluripotent stem cells and (iii) adult stem cells including hematopoietic stem cells, neural stem cells and mesenchymal stem cells.

2The therapeutic potential of stem cells can be attributed to three key mechanisms of action. The first is “homing”, for which systemically administered stem cells migrate to the focus of acute injury due to chemical gradients. It is hypothesized that migration to target tissues occurs through a process similar to that of leukocyte migration. Chemoattraction is mediated by cell surface receptors such as the chemokine receptors. Although the exact mechanism of stem cell-endothelial interaction at the target site is not well established, integrins and selectins mediate these interactions. Transmigration of stem cells to the focus of injury occurs across the endothelium via leukocyte-like pathways involving vascular cell adhesion molecule 1 (VCAM-1) and G-protein-coupled receptor signaling. The second mechanism is differentiation into multiple cell types, which locally engraft and induce restoration of function by augmenting or replacing damaged tissues. The third major mechanism is secretion of bioactive factors, which may potentially affect both local and systemic physiological processes.

3Adult stem cells guarantee the maintenance and repair of adult tissues and organs. Mesenchymal stem cells (MSCs) are especially emerging as cell-based therapy of numerous diseases.

2. Mesenchymal Stem Cells (MSCs)

4Adult bone marrow MSCs (BMMSCs) were discovered in 1968 by Friedenstein et al., who described a fibroblast-like population able to secrete growth factors and cytokines relevant for hematopoiesis and others processes. MSCs have an apparently ubiquitous localization. They have also been isolated from other adult tissues such as adipose tissue, skin, lung, synovial membrane, dental pulp, nasal olfactory mucosa, breast milk, scalp tissue, muscle, periosteum, corneal limbus, peripheral blood, endometrial and menstrual blood, and uterine cervix, as well as from fetal/neonatal tissues. All of these MCSs can be isolated and expanded from stroma of many tissues, the bone marrow and subcutaneous fat being the preferred sources. The Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy established in 2006 the minimal identifying characteristics for human MSCs: (a) plastic-adherent cells when maintained in standard culture conditions; (b) expression of CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79a or CD19 and HLA-DR surface molecules and (c) capacity to differentiate into osteoblasts, adipocytes and chondroblasts in vitro.

5Although MSCs are present in multiple tissues, their overall quantity in the body is scarce. Cell therapy protocols generally require hundreds of millions of MSCs per treatment; therefore, cell expansion in vitro is needed for about 10 weeks before implantation. The patient’s age and clinical characteristics influence the optimal culture conditions for clinical scale production of human MSCs. The cellular senescence of MSCs in vitro contributes to aging and age-related diseases.

6Earlier research attributed the therapeutic effects of MSCs to their engrafting and differentiation capacity. However, several studies have revealed that the implantation time of MSCs is usually too short to have an effective impact. Indeed, it has been reported that <1% MSCs survive for more than one week after systemic administration, suggesting that the main effects of MSCs are probably mediated by paracrine mechanisms. Recent studies have also brought attention to the wide array of bioactive factors produced by MSCs, which may play an important role in the regulation of numerous physiological processes. Therefore, the secretome from MSCs has attracted much attention for its potential use in tissue repair and regeneration.

3. Secretome and Conditioned Media from MSCs as New Therapeutic Strategy

7We are presently witnessing the emergence of a novel type of biological regulation involving the communication between cells via their secreted substances, the secretome. The secretome is defined as the set of factors/molecules secreted to the extracellular space. These factors include, among others, soluble proteins, free nucleic acids, lipids and extracellular vesicles. The latter can be subdivided into apoptotic bodies, microparticles and exosomes. The secretome of individual cells and tissues is specific, and changes in response to fluctuations in physiological states or pathological conditions.

8The use of cell-free therapies such as MSC-sourced secretome in regenerative medicine provides key advantages over stem-cell based applications: (a) application of the secretome resolves several safety considerations potentially associated with the transplantation of living and proliferative cell populations including immune compatibility, tumorigenicity, emboli formation and the transmission of infections; (b) MSC-sourced secretome may be evaluated for safety, dosage and potency in a manner analogous to conventional pharmaceutical agents; (c) storage can be done without application of potentially toxic cryopreservative agents for a long period without loss of product potency; (d) using MSC-sourced secretome, such as conditioned medium (CM), is more economical and more practical for clinical application since it avoids invasive cell collection procedures; (e) mass-production is possible through tailor-made cell lines under controlled laboratory conditions, providing a convenient source of bioactive factors; (f) the time and cost of expansion and maintenance of cultured stem cells could be greatly reduced and off-the-shelf secretome therapies could be immediately available for treatment of acute conditions such as cerebral ischemia, myocardial infarction, or military trauma; and (g) finally, the biological product obtained for therapeutic applications could be modified to desired cell-specific effects.

9CM represents the complete regenerative milieu of cell-sourced secretome and vesicular elements. The soluble components of the secretome may be separated from the microvesicle fraction by centrifugation, filtration, polymer precipitation-based methodologies, ion exchange chromatography and size-exclusion chromatography. Both of these components may be capable of independently triggering regeneration and repair as well as of mediating the de novo organogenesis of tissue-engineered organs ex vivo.

10It has been demonstrated that MSC-derived CM is sufficient to significantly improve multiple biomarkers of pathophysiology, and, in general, to be as effective as transplantation of the corresponding MSCs in a long list of animal models (Table 1).

4.1. Immunomodulation and Antiinflammatory Activity

11MSCs affect the proliferation, activation and function of immune cells. Pre-clinical studies on animal models have shown a suppressive effect on both innate and adaptive immunity. In addition, there is extensive clinical experience on MSCs based on interventional clinical studies (http://clinicaltrials.gov). The most promising potential applications involve the treatment of graft versus host disease, as well as of autoimmune and inflammatory diseases, such as insulin systemic lupus erythematosus (SLE), diabetes mellitus type I, (SLE), multiple sclerosis or Crohn’s disease. Interestingly, MSCs typically express major histocompatibility complex (MHC) -I but lack expression of MHC-II, CD40, CD80, and CD86 on the cell surface, and thus they escape T cell recognition and often fail to induce an immune response by the transplant host. It has been widely shown that MSCs are capable of affecting activation and proliferation of all immune cell types. Di Nicola et al. found that MSCs inhibit proliferation of CD4+ and CD8+ T cells. In addition, MSCs act in three major stages of immune response: antigen recognition and presentation; T cell activation, proliferation, and differentiation; and the T-cell effector stage. Our studies have also demonstrated an inhibitory effect of the CM from human uterine cervical stem cells (hUCESC-CM) on monocyte–macrophage differentiation as well as on macrophage–monocyte de-differentiation.

12It is well established that the antiinflammatory effect of MSC-CM is at least in part mediated by soluble immunoregulatory molecules. Among the antiinflammatory cytokines present in MSC-CM are tumor necrosis factor β1 (TGFβ1), interleukin (IL) 13, IL18 binding protein (IL18BP), ciliary neurotrophic factor (CNTF), neurotrophin 3 (NT-3) factor, IL10, IL12p70, IL17E, IL27 or IL1 receptor antagonist (IL1RA). MSC-CM has also been found to contain pro-inflammatory cytokines, such as IL1b, IL6, IL8 and IL9. The balance between these anti-inflammatory and pro-inflammatory cytokines may determine the final effect. Nevertheless, it is also remarkable that MSCs inhibit proinflammatory cytokines, such as interferon (IFN)-γ and tumor necrosis factor α (TNFα), while increasing antiinflammatory IL10 release. Our recent findings derived from an experimental model of uveitis in rats corroborate this. We found that hUCESC-CM treatment significantly reduced mRNA expression of IL6, IL8, TNFα and MIP-1α pro-inflammatory cytokines, but increased mRNA expression of the IL10 anti-inflammatory cytokine, which is similar to results using MSC-CM from amniotic fluid in a mice colitis model. We also found that hUCESC-CM reduces the infiltration of leucocytes in ocular tissues.

4.2. Anti-Apoptotic Activity

13MSCs prevent cell death via restoration of local microenvironment by producing inhibitor proteins of apoptosis and by decreasing expression of anti-apoptotic proteins. Thus, it was reported that MSCs decrease the pro-apoptotic factors Bax and cleaved caspase-3 expression but increase the anti-apoptotic Bcl-2 levels, while expression of pro-angiogenic factors, such as basic fibroblastic growth factor (bFGF), vascular endothelial growth factor (VEGF), and CXCL12 were increased in MSC-treated hearts compared to medium-treated hearts. It is worth noting that our team has found that hUCESC-CM has a different effect on normal cells than on cancer cells. While an antiapoptotic effect was observed in normal cells, we found that hUCESC-CM induced apoptosis in cancer cells both in vitro and in vivo.

4.3. Wound Healing and Tissue Repair

14A beneficial role on wound healing and tissue repair was observed by MSCs at the site of injury. Data from animal models seem to indicate that autocrine or paracrine effects of MSCs rather than their direct engraftment and tissue differentiation may play the key role in wound healing. Recently, we reported the efficacy of hUCESC-CM on epithelial healing in a rat model of dry eyes after alkaline corneal epithelial ulcer induction. After injury, dry eyes treated with hUCESC-CM improved epithelial regeneration and induced reduced corneal MIP-1α and TNF-α mRNA expression. Corneal avascularity is required for optical transparency, so it is relevant that hUCESC-CM treatment did not produce vascularization in this model. Inflammation, chemical burns and corneal infections induce leukocytes to infiltrate the cornea, which induce corneal neovascularization by releasing inflammatory cytokines.

15Several studies have reported the presence of growth factors in MSC-CM that contribute to the regeneration of damaged organ tissues, with special emphasis on proliferation. It is also worth mentioning that secretome from MSCs has anti-fibrotic and angiogenic effects that can reduce scar formation and improve the long-term ejection fraction when administered early or prior to adverse remodeling in experimental models of myocardial infarction.

4.4. Neuroprotective and Neurotrophic Effects

16Over the past decade, numerous studies have appeared supporting the neuroprotective and neurotrophic effects of MSC-secretome. In fact, it is known that MSC-CM contains a number of neurothophic factors. Several studies have reported beneficial effects of MSC-based approaches on nerve injury models. These effects include modulation of the inflammatory environment on the site, enhanced vascularization of the regenerating site, increased thickness of the myelin sheaths, modulation of the Wallerian degeneration stage, accelerated fibre regeneration and increase in the number thereof, reduction of fibrotic scaring, and improved fibre organization.

17A key role of MSC secretome as a modulator of the neurogenic niche has been recently reported. Both neural stem cells (NSCs) and MSCs secrete a panel of growth factors. Likewise, mutually beneficially effects have been shown when these cell types are co-cultured in vitro.

18Beneficial effects of CM derived from stem cells of human exfoliated deciduous teeth (SHEDs) in an animal model of Alzheimer’s disease have recently been reported. Intranasal administration of SHEDs improved cognitive function and induced neuroregenerative effects such as an attenuated pro-inflammatory response induced by amyloid plaques, and anti-inflammatory M2-like microglia.

4.5. Angiogenesis Regulation

19Angiogenesis is defined as the process by which new vasculature sprouts from pre-existing blood vessels. Normal angiogenesis is important during wound healing process. Various studies have demonstrated the effect of MSC secretome on key steps in angiogenesis. For example, different MSC populations (e.g., adipose, amniotic, bone marrow (BM) and Wharton jelly umbilical vein) induce proliferation and migration of endothelial cells promoting tube formation, as well as prevent endothelial cell apoptosis in vitro.

20The role of MSCs in angiogenesis is of great interest given the large spectrum of clinical diseases related to insufficient or abnormal vessel growth, including atherosclerotic diseases and wound healing disorders. Successful application of MSCs to promote angiogenesis in different animal models of cerebral ischemia/stroke, myocardial infarction, neurogenic bladder, peripheral artery disease, and stress urinary incontinence has been demonstrated.

21A number of angiogenic stimulators and inhibitors have been identified in MSC secretome. Recently, an extensive proteomic analysis of the MSC-CM stimulated with inflammatory cytokines led to the identification of tissue inhibitor of metalloproteinase-1 (TIMP-1) as the molecule responsible for the antiangiogenic effects of MSCs. All of these data indicate that various factors present in MSC-CM may represent a balanced cocktail that acts in concert to promote angiogenesis. Moreover, several studies demonstrate that the secretion of these pro- and anti-angiogenic factors can be modified depending on chemokines and hypoxic conditions. Thus, TGFα had the ability to increase the level of several growth factors (i.e., VEGF, hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), IL6 and IL8). Likewise, CM from MSCs treated with TFG-α induces blood vessel growth in an in vivo assay.

4.6. Antitumor Effect

22Various studies have paid attention to the relationship between MSCs and the oncogenic process. Basically, the role of MSCs in cancer could be carried out as: (a) an indirect effect, via modulatory effect of MSCs on tumors; (b) as a direct effect, via malignant transformation of the MSCs themselves. Contradictory results have been described regarding pro- or anti-tumor effect induced by MSCs, both in vitro and in vivo. These discrepancies about MSC functionality might be due to the absence of specific markers to isolate more homogeneous population. Contradictory results have been also reported with respect to MSC-CM. For example, BMMSC-CM has either anti-tumor effects on non-small cell lung cancer cells or stimulatory effects on myeloma cells, whereas adipose stem cell conditioned medium (ADSC-CM) has no effect on human glioblastoma cancer stem cell subpopulations. Specific anti-tumor effects of hUCESC-CM on proliferation, apoptosis, and tumor-cell invasiveness have been demonstrated. hUCESC-CM inhibits the aggressive behavior of breast cancer cells in vitro (cell lines and primary tumors) and reduces tumor growth in vivo in a mouse xenograft tumor model. These findings differ from those obtained using other types of MSC-CM. Compared to adipose stem cell conditioned medium (ADSC-CM), hUCESC-CM contains low levels of factors involved in cancer progression, e.g., EGFR, FGF-4 and -9, intracellular adhesion molecule-3, IL6, IL6R, CCL7, macrophage migration inhibitory factor (MIF), soluble gp130 and VEGF-D. On the other hand, hUCESC-CM contains high levels of factors involved in inhibition of cancer progression, e.g., tumor necrosis factor superfamily member 14 (LIGHT), Fms-related tyrosine kinase 3 ligand (FLT-3 ligand), CXCL10, and latency-associated protein (LAP). These findings support the hypothesis that the effect of CM from MSCs could depend on its origin. Interestingly, our results also indicate that hUCESC-CM exerts no action on low-proliferating breast cancer epithelial cells (MCF7 cell line), while exerting high anti-tumor activity against highly proliferating and metastasis-producing breast cancer cells (MDA-MB-231 cell line). As previously hypothesized, it is not surprising that the human uterine cervix might be a reservoir of MSCs with precise site-specific functions. In fact, it is known that fundamental biological events, some of them crucial for the host’s wellbeing, take place in the cervical transformation zone. Furthermore, inflammation and regeneration are closely linked in this setting, which constitute a standard model of carcinogenesis. Therefore, it can be hypothesized that hUCESCs (and their CM) have intrinsic defense mechanisms against inherent vulnerability from malignant transformation. hUCESCs might also proceed as “guardians of their environment” avoiding the acquisition of a malignant phenotype by adult cells, modulating their proliferation rate and inducing apoptosis if they become dangerous for the host.

23It has also been reported that hUCESC-CM inhibits proliferation and invasion of cancer associated fibroblasts (CAFs). This is relevant because CAFs, a prevailing component of tumor stroma, contribute to tumor growth, invasion and dissemination. CAFs promote tumor initiation and progression through the stimulation of angiogenesis, invasion, and metastasis, but also mediating drug resistance, which leads to considering them a therapeutic target in current clinical trials. Another important cellular component of tumor microenvironment are tumor associated macrophages (TAMs), which are a relevant inhibitor of anti-tumor immunity and a crucial barrier to successful immunotherapy. In addition, TAM infiltration is associated with poor prognosis in solid tumors, including breast cancer, thus the relevance of our data showing that hUCESC-CM significantly inhibits and reverts monocyte to macrophage differentiation.

4.7. Antimicrobial Effect

24Several in vivo studies have shown beneficial effects of MSC treatment in bacteria-induced sepsis, suggesting immunomodulatory properties of MSCs mediated by enhanced phagocyte activity. Our in vitro studies have demonstrated that hUCESC-CM have a bactericidal effect on both E. coli and S. epidermidis. In addition, hUCESC-CM has at least the same bactericidal effect as commercial solutions against S. epidermidis in infected contact lenses. Given that these experiments were carried out in vitro and the immune response of the host cells were not involved in the process, one or more substances present in hUCESC-CM must be responsible for this antibacterial effect, such as the chemokines CXCL10, CXCL8, CXCL1, CXCL6, CCL20, and CCL5, which are present in higher levels in hUCESC-CM. These chemokines are known to have antibacterial effects against E. coli and different strains of Staphylococcus, which lead to consideration that a paracrine signaling might be implicated in the antibacterial potential of hUCESC-CM.

5. Differences in MSC-CM Composition and Need for Standardization

25Although different MSC populations are known to share phenotypic characteristics and show regenerative potential, they reside in different anatomic locations and their secretome is likely to vary. Differences in therapeutic potential according to MSC origin have been demonstrated. For example, while ADSC-CM is positive for HGF, VEGF, stem cell factor (SCF) and nerve growth factor (NGF), CM of human umbilical cord perivascular cells (hUCPVC-CM) only presents NGF and VEGF. Likewise, differences have been shown in the composition of ADSC-CM and adult bone marrow MSCs (BMMSC) -CM, as well as in secreted factors from Wharton’s jelly and BMMSCs. Recently, Pires et al. found important changes in the secretome of MSCs from BM, adipose tissue, and umbilical cord after a comparative proteomic based analysis by mass spectrometry. In order to standardize the production of CM from each MSC type, further studies are necessary with regard to culture medium and supplements, culture duration, and culture conditions.

6. Exosomes from MSCs

26The term exosome generally refers to a specific class of lipid-membrane bound extracellular vesicle characterized by a diameter of 40–150 nm and a density of 1.09–1.18 g/mL. Increasing evidence indicates that MSCs produce massive amounts of exosomes in comparison with other cells, and that many of the regenerative properties previously credited to stem cells are being shown to be mediated through secreted exosomes. Exosomes may subsequently be internalized by other cells principally by phagocytosis, fusion with the cell membrane and receptor–ligand interaction, allowing the release of their contents into the cytoplasm. It has been reported that treatment with MSC-derived exosomes and microvesicles improves at least one clinically relevant parameter associated with organ functionality (Table 2). The regenerative potential of exosomes may be modulated by a variety of mechanisms, such as the prior exposure of the originating cell population to external stimuli—for example, inflammatory conditioning of human umbilical cord blood-derived MSCs (hUCBSCs) with IFN-γ results in MSCs being less able to protect against acute ischemic renal injury in vivo than their unconditioned counterparts.

27Several specific advantages of using exosomes instead of CM for regenerative therapy have been reported. Through encapsulation, therapeutically relevant molecules (proteins and nucleic acids) are protected from degradation. In this sense, MSC can be engineered to produce exosomes having the mRNA information of relevant gene in the cargo and therefore retaining the ability to home to tumor or disease site, and thus be internalized by the targeted cells. The loading of an intracellular miRNA into exosomes could be done by engineering an extra-seed sequence (hEXO motif), which opens the way for the selective modification of the miRNA exosomal cargo. In fact, it has recently been reported that in a mouse model of Huntington’s Disease, exosomes loaded with modified small interfering RNAs (hsiRNAs) targeting Huntingtin mRNA were internalized by primary cortical neurons and were able to induce mRNA and protein silencing. From a manufacturing perspective, exosomes last a long time and may be stored in much smaller volumes than CM. However, potential risks associated with exosome based therapies have also been reported, such as the uncontrolled transfer of genetic information between cell populations. In addition, exosomes can modulate immune response through transport and presentation of key antigens. Another potential toxicity associated with exosome-based therapies is biodistribution. Bioluminescence analysis in mice of intravenously delivered, luciferase-labeled exosomes showed strong localization to the spleen, liver, lung and kidney, and possibly brain, heart and muscle within 30 min of injection, prior to spiking in the urine at 60 min post-delivery. A clear understanding of the relationships between delivery site, dosage, biodistribution and clearing dynamics is essential for ensuring product biosafety.

28Other important aspects of MSC exosomes are their tissue-specific responses by directing informational molecules to target cells, and the possibility to act as reservoir of biomarkers, which can differ depending on their sources of isolation. For instance, exosomes from ADSC appear to be more effective in degrading Aβ compared to BMMSC-derived exosomes in an in vitro model of Alzheimer’s disease. Likewise, it has been described that exosomes from ADSC has a therapeutic potential for treating Huntington’s Disease decreasing aggregation of mutant Huntingtin, ameliorating abnormal apoptotic protein level and reducing mitochondrial dysfunction. There is greater neurite outgrowth response from exosomes released by menstrual fluid derived MSCs than from umbilical cord, chorion and BM-derived MSCs. These findings suggest the need for further research into the functional properties of exosomes released by MSCs isolated from adult tissues of different sources, and the influence of gender on secretion profile.

7. Clinical Studies with Secretome from MSCs

29A limited number of human clinical studies are already available on the use of secretome products from MSCs. Application of allograft ADSC-CM, after the treatment of fractional carbon dioxide laser resurfacing on human skin, enhances wound healing by the reduction of adverse effects such as hyperpigmentation, erythema and increased transepidermal water loss. Likewise, intradermal injection of ADSC-CM into the scalp of alopecia patients using a split-scalp study design significantly promoted hair growth in both male and female patients. Similarly, a retrospective and observational study of female pattern hair loss treated with ADSC-CM showed efficacy after 12 weeks, significantly increasing both hair density and thickness. None of the patients reported severe adverse reactions. Finally, BMMSC-CM has also been used safely to improve alveolar bone regeneration.

30Several clinical applications of MSC-derived exosomes have been reported. A preliminary study demonstrated that increasing dosage of MSC-derived exosomes in a patient with severe treatment-refractory graft-versus-host grade IV disease, affecting skin and intestinal tract, was well tolerated and showed a significant and sustainable improvement of symptoms, which remained stable for five months. Another clinical trial applied MSC-derived exosomes for improving β-cell mass in type 1 diabetes mellitus patients (https://clinicaltrials.gov/ct2/show/NCT02138331?term=MSC+exosomes&rank=1). Many more studies are expected to be initiated shortly.

8. Scalable Production of MSC Secretome

31There is presently a lack of current good manufacturing practice (cGMP) guidelines for large-scale manufacturing of MSC-derived products. It has been estimated that hundreds of micrograms to milligram of exosomes may be needed to treat patients in a clinical trial. Senescence of MSCs represents an intrinsic limitation on production capacity. Cell immortalization is one approach to this issue. Indeed, an efficient strategy could be MYC proto-oncogene transformation to ensure an infinite supply of cells for production. A bioreactor approach could eliminate the need for continuous passage of cells during production runs, thus alleviating the need for plastic vessels and medium. A combination of methodologies for isolating exosomes might also prove helpful.

9. Inducing Secretory Modifications in MSCs

32There is evidence suggesting that modification of MSCs could improve the therapeutic effect of their secretome. A variety of stimuli and conditions have been advanced including: (a) cell culture under hypoxic conditions, which increases the production of growth factors and anti-inflammatory molecules; (b) pro-inflammatory stimuli, which induces higher secretion of immune-related factors; (c) tri-dimensional growth, which upregulates production of anti-tumoral and anti-inflammatory factors; and (d) microparticle engineering.

9.1. Hypoxia

33In a variety of tissues, reduction of oxygen tension activates the hypoxia inducible factor (HIF-1α), inducing in turn, the expression of angiogenic factors such as VEGF. It has been recently demonstrated that cell culture under hypoxic conditions has beneficial effects on MSCs. In fact, it is known that most growth factors are upregulated in various stem cells under hypoxia conditions. In addition, hypoxia allows for maintaining an undifferentiated phenotype of MSCs for self-renewal. This may be because MSCs usually are found in hypoxic areas of the body, poorly perfused by the circulatory system. Accordingly, several studies have shown the negative influence of ambient O2 concentration on MSCs, inducing early senescence, longer population doubling time and DNA damage. For example, a 3% O2 tension in cell culture has shown positive effects on in vitro survival and self-renewal of BMMSCs, while maintaining their undifferentiated state. Likewise, a 2% O2 tension was found to preserve stemness and enhance proliferation and angiogenic potential of ADSCs. It has recently been reported that hypoxic human dental pulp stem cells (DPSCs) are smaller in size and exhibit larger nuclei than those grown in normoxic environment. On the other hand, culture of DPSCs in 5% O2 significantly increases their migration and proliferation rate, but also the expression of stem cell markers and BDNF, NGF, SOX2 and VEGF. All these data suggest that adequate O2 concentrations may enhance MSCs properties and growth, and trophic effect of their secretome.

34Treatment with hypoxic-preconditioned ADSC-CM increased the viability of hepatotoxic hepatocytes and enhanced liver regeneration in partially hepatectomized mice. Therapeutic benefits of hypoxia have also been reported in a rat model of traumatic brain injury and of diabetic cardiopathy.

9.2. Pro-Inflammatory Stimuli

35Evidence suggests that stimulation of MSCs by inflammatory factors enhances their regenerative potential and improves their anti-inflammatory response. Thus, exposure of MSCs to IFN-γ stimulates indoleamine-pyrrole 2,3-dioxygenase (IDO) enzyme production, which increases immune suppressive activity of MSCs. It has also been reported that pretreatment of MSCs with TNF-α increases their angiogenic activity in vitro and in vivo in an animal model of limb ischemia. Pre-treatment of MSCs with TNF-α also increases proliferation, migration, and osteogenic differentiation through up-regulation of bone morphogenetic protein-2 (BMP-2). Likewise, the regenerative activity of MSCs can be stimulated by lipopolysaccharide (LPS) or toll-like receptors (TLR) agonists through induction of paracrine factors production.

9.3. Tri-Dimensional Growth

36MSCs are typically grown in vitro in monolayer systems. Nevertheless, tri-dimensional cultures, such as spheroid culture, have shown to stimulate trophic factors secretion. Spheroid cultures need special handling and equipment (spinner flask) but yield more cells compared to conventional monolayer cultures, and therefore more secreted factors. It is worth mentioning that cells located at the center of the spheroid may be in relative hypoxic condition compared to cells on the surface. As mentioned above, oxygen concentration is a critical environmental factor that affects the maintenance of stem cell plasticity and proliferation. CM from human MSC spheroids has been found to inhibit TNF-α, CXCL2, IL6, IL12p40, and IL23 production from LPS-stimulated macrophages and stimulate higher production of prostaglandin E2 (PGE2). In a murine model of zymosan-induced peritonitis, spheroids and spheroid-derived cells have more effective anti-inflammatory effects than monolayer MSC culture cells. Hanging-drop-induced MSC spheres (containing 25,000 cells per drop) produced higher levels of TNF-α-stimulated gene 6 protein (TSG-6), an important anti-inflammatory factor. They also produced higher level of stanniocalcin-1 (STC1), an anti-inflammatory and antiapoptotic protein, as well as three anticancer proteins. Dynamic cultures using spinner flasks or rotating wall vessel bioreactors form small spheroids and have demonstrated better adipogenic and osteogenic differentiation and also a higher expression of IL24.

9.4. Microparticle Engineering

37Certain properties of CM can be modified via microparticle engineering. It has recently been reported that microparticles loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1), an NF-κB inhibitor, can attenuate the secretion by MSCs of pro-inflammatory factors for at least six days in vitro. CM derived from TPCA-1-loaded MSCs also showed reduced ability to attract human monocytes and prevented differentiation of human cardiac fibroblasts to myofibroblasts. This is an interesting finding because adverse remodeling or cardiac fibrosis due to differentiation of cardiac fibroblasts into myofibroblasts with pro-inflammatory phenotype and collagen deposition is the leading cause for heart failure.

10. Conclusions

38MSCs have drawn much interest for their therapeutic benefits in immune modulation and tissue remodeling. Earlier research primarily attributed this to the ability of transplanted MSCs to engraft and to differentiate into multiple tissue types. However, there are several limitations that currently impair the wide widespread use of MSCs. Some studies suggest that the transportation of MSCs into normal tissues might cause tumor formation. Recent studies have revealed that implanted MSCs do not survive for long, suggesting that the benefits of MSC therapy might be attributable to their secreted factors. An expanding body of recent literature has brought attention to the vast array of bioactive factors produced by MSCs including cytokines, growth factors, microRNAs, proteasomes, and exosomes, which may play an important role in the regulation of numerous physiological processes. Secretome-based approaches using CM or exosomes may present considerable potential advantages over living cells in terms of manufacturing, storage, handling, product shelf life and their potential as a ready-to-go biological therapeutic agent. Multiple experimental studies demonstrate that secretome-derived products are sufficient to significantly improve multiple biomarkers of pathophysiology in many animal models of different diseases. However, composition and effects of secretomes differ based on MSC anatomical origin. Using hUCESCs, in particular, presents important advantages. hUCESCs are obtained by Pap cervical smear, which is a less invasive and painful method than those used for obtaining other MSCs (e.g., bone marrow or adipose tissue). In addition, due to their easy isolation and high proliferative rate, it is possible to quickly obtain large amounts of hUCESCs or secretome-derived products for research and clinical use.

39Considering that multiple clinical trials involving MSCs have been approved by national agencies, it is perfectly reasonable to expect approval of secretome-derived products from MSCs. Although the composition of secretome-derived products from MSCs is complex, this in itself should not be an impediment for regulatory approval of a regenerative product. For example, platelet-rich plasma or amniotic fluid, which are highly complex and include numerous growth factors and exosomes that remain poorly characterized, are routinely used as a regenerative therapy for multiple applications in wound healing and orthopedics. Exosomes sourced from dendritic cells have already reached the clinical-trial stage for immunotherapy of certain cancers. Nevertheless, regulatory requirements for manufacturing and quality control will be necessary to establish the safety and efficacy profile of these products.

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9.
Friedenstein A.J., Chailakhjan R.K., Lalykina K.S. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet. 1970;3:393-403.
Not in our library10.1111/j.1365-2184.1970.tb00347.x
10.
De Ugarte D.A., Alfonso Z., Zuk P.A., Elbarbary A., Zhu M., Ashjian P., Benhaim P., Hedrick M.H., Fraser J.K. Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow. Immunol. Lett. 2003;89:267-270.
Not in our library10.1016/s0165-2478(03)00108-1
11.
Orciani M., di Primio R. Skin-derived mesenchymal stem cells: Isolation, culture, and characterization. Methods Mol. Biol. 2013;989:275-283.
Not in our library10.1007/978-1-62703-330-5_21
12.
Hua J., Yu H., Dong W., Yang C., Gao Z., Lei A., Sun Y., Pan S., Wu Y., Dou Z. Characterization of mesenchymal stem cells (MSCs) from human fetal lung: Potential differentiation of germ cells. Tissue Cell. 2009;41:448-455.
Not in our library10.1016/j.tice.2009.05.004
13.
De Bari C., Dell’Accio F., Tylzanowski P., Luyten F.P. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001;44:1928-1942.
Not in our library10.1002/1529-0131(200108)44:8<1928::aid-art331>3.0.co;2-p
14.
Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo · 2000
Not checked
15.
Delorme B., Nivet E., Gaillard J., Haupl T., Ringe J., Deveze A., Magnan J., Sohier J., Khrestchatisky M., Roman F.S., et al. The human nose harbors a niche of olfactory ectomesenchymal stem cells displaying neurogenic and osteogenic properties. Stem Cells Dev. 2010;19:853-866.
Not in our library10.1089/scd.2009.0267
16.
Patki S., Kadam S., Chandra V., Bhonde R. Human breast milk is a rich source of multipotent mesenchymal stem cells. Hum. Cell. 2010;23:35-40.
Not in our library10.1111/j.1749-0774.2010.00083.x
17.
Shih D.T., Lee D.C., Chen S.C., Tsai R.Y., Huang C.T., Tsai C.C., Shen E.Y., Chiu W.T. Isolation and characterization of neurogenic mesenchymal stem cells in human scalp tissue. Stem Cells. 2005;23:1012-1020.
Not in our library10.1634/stemcells.2004-0125
18.
Zheng B., Cao B., Crisan M., Sun B., Li G., Logar A., Yap S., Pollett J.B., Drowley L., Cassino T., et al. Prospective identification of myogenic endothelial cells in human skeletal muscle. Nat. Biotechnol. 2007;25:1025-1034.
Not in our library10.1038/nbt1334
19.
De Bari C., Dell’Accio F., Luyten F.P. Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age. Arthritis Rheum. 2001;44:85-95.
Not in our library10.1002/1529-0131(200101)44:1<85::aid-anr12>3.0.co;2-6
20.
Joe A.W., Yeung S.N. Concise review: Identifying limbal stem cells: Classical concepts and new challenges. Stem Cells Transl. Med. 2014;3:318-322.
Not in our library10.5966/sctm.2013-0137
21.
Villaron E.M., Almeida J., Lopez-Holgado N., Alcoceba M., Sanchez-Abarca L.I., Sanchez-Guijo F.M., Alberca M., Perez-Simon J.A., san Miguel J.F., del Canizo M.C. Mesenchymal stem cells are present in peripheral blood and can engraft after allogeneic hematopoietic stem cell transplantation. Haematologica. 2004;89:1421-1427.
Not in our library
22.
Ulrich D., Muralitharan R., Gargett C.E. Toward the use of endometrial and menstrual blood mesenchymal stem cells for cell-based therapies. Expert Opin. Biol. Ther. 2013;13:1387-1400.
Not in our library10.1517/14712598.2013.826187
23.
Eiro N., Sendon-Lago J., Seoane S., Bermudez M.A., Lamelas M.L., Garcia-Caballero T., Schneider J., Perez-Fernandez R., Vizoso F.J. Potential therapeutic effect of the secretome from human uterine cervical stem cells against both cancer and stromal cells compared with adipose tissue stem cells. Oncotarget. 2014;5:10692-10708.
Not in our library10.18632/oncotarget.2530
24.
Igura K., Zhang X., Takahashi K., Mitsuru A., Yamaguchi S., Takashi T.A. Isolation and characterization of mesenchymal progenitor cells from chorionic villi of human placenta. Cytotherapy. 2004;6:543-553.
Not in our library10.1080/14653240410005366-1
25.
De Coppi P., Bartsch G., Siddiqui M.M., Xu T., Santos C.C., Perin L., Mostoslavsky G., Serre A.C., Snyder E.Y., Yoo J.J., et al. Isolation of amniotic stem cell lines with potential for therapy. Nat. Biotechnol. 2007;25:100-106.
Not in our library10.1038/nbt1274
26.
Wang H.S., Hung S.C., Peng S.T., Huang C.C., Wei H.M., Guo Y.J., Fu Y.S., Lai M.C., Chen C.C. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells. 2004;22:1330-1337.
Not in our library10.1634/stemcells.2004-0013
27.
Bieback K., Kern S., Kluter H., Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells. 2004;22:625-634.
Not in our library10.1634/stemcells.22-4-625
28.
Crisan M., Yap S., Casteilla L., Chen C.W., Corselli M., Park T.S., Andriolo G., Sun B., Zheng B., Zhang L., et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3:301-313.
Not in our library10.1016/j.stem.2008.07.003
29.
Dominici M., le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F., Krause D., Deans R., Keating A., Prockop D., Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 2006;8:315-317.
Not in our library10.1080/14653240600855905
30.
Sotiropoulou P.A., Perez S.A., Salagianni M., Baxevanis C.N., Papamichail M. Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells. 2006;24:462-471.
Not in our library10.1634/stemcells.2004-0331
31.
Duggal S., Brinchmann J.E. Importance of serum source for the in vitro replicative senescence of human bone marrow derived mesenchymal stem cells. J. Cell. Physiol. 2011;226:2908-2915.
Not in our library10.1002/jcp.22637
32.
Baker N., Boyette L.B., Tuan R.S. Characterization of bone marrow-derived mesenchymal stem cells in aging. Bone. 2015;70:37-47.
Not in our library10.1016/j.bone.2014.10.014
33.
Muller-Ehmsen J., Whittaker P., Kloner R.A., Dow J.S., Sakoda T., Long T.I., Laird P.W., Kedes L. Survival and development of neonatal rat cardiomyocytes transplanted into adult myocardium. J. Mol. Cell. Cardiol. 2002;34:107-116.
Not in our library10.1006/jmcc.2001.1491
34.
Toma C., Wagner W.R., Bowry S., Schwartz A., Villanueva F. Fate of culture-expanded mesenchymal stem cells in the microvasculature: In vivo observations of cell kinetics. Circ. Res. 2009;104:398-402.
Not in our library10.1161/circresaha.108.187724
35.
Ide C., Nakai Y., Nakano N., Seo T.B., Yamada Y., Endo K., Noda T., Saito F., Suzuki Y., Fukushima M., et al. Bone marrow stromal cell transplantation for treatment of sub-acute spinal cord injury in the rat. Brain Res. 2010;1332:32-47.
Not in our library10.1016/j.brainres.2010.03.043
36.
Chimenti I., Smith R.R., Li T.S., Gerstenblith G., Messina E., Giacomello A., Marban E. Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Circ. Res. 2010;106:971-980.
Not in our library10.1161/circresaha.109.210682
37.
Timmers L., Lim S.K., Hoefer I.E., Arslan F., Lai R.C., van Oorschot A.A., Goumans M.J., Strijder C., Sze S.K., Choo A., et al. Human mesenchymal stem cell-conditioned medium improves cardiac function following myocardial infarction. Stem Cell Res. 2011;6:206-214.
Not in our library10.1016/j.scr.2011.01.001
38.
Lee R.H., Pulin A.A., Seo M.J., Kota D.J., Ylostalo J., Larson B.L., Semprun-Prieto L., Delafontaine P., Prockop D.J. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5:54-63.
Not in our library10.1016/j.stem.2009.05.003
39.
Parekkadan B., Milwid J.M. Mesenchymal stem cells as therapeutics. Annu. Rev. Biomed. Eng. 2010;12:87-117.
Not in our library10.1146/annurev-bioeng-070909-105309
40.
Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion · 2012
No notice
41.
Toma C., Pittenger M.F., Cahill K.S., Byrne B.J., Kessler P.D. Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation. 2002;105:93-98.
Not in our library10.1161/hc0102.101442
42.
Song Y.S., Lee H.J., Doo S.H., Lee S.J., Lim I., Chang K.T., Kim S.U. Mesenchymal stem cells overexpressing hepatocyte growth factor (HGF) inhibit collagen deposit and improve bladder function in rat model of bladder outlet obstruction. Cell Transplant. 2012;21:1641-1650.
Not in our library10.3727/096368912x637488
43.
Maguire G. Stem cell therapy without the cells. Commun. Integr. Biol. 2013;6:e26631.
Not in our library10.4161/cib.26631
44.
A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods · 2014
No notice
45.
Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing · 2008
Corrected
46.
Ciapetti G., Granchi D., Baldini N. The combined use of mesenchymal stromal cells and scaffolds for bone repair. Curr. Pharm Des. 2012;18:1796-1820.
Not in our library10.2174/138161212799859648
47.
Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy · 2012
No notice
48.
Beer L., Mildner M., Ankersmit H.J. Cell secretome based drug substances in regenerative medicine: When regulatory affairs meet basic science. Ann. Transl. Med. 2017;5:170.
Not in our library10.21037/atm.2017.03.50
49.
Bermudez M.A., Sendon-Lago J., Eiro N., Trevino M., Gonzalez F., Yebra-Pimentel E., Giraldez M.J., Macia M., Lamelas M.L., Saa J., et al. Corneal epithelial wound healing and bactericidal effect of conditioned medium from human uterine cervical stem cells. Invest. Ophthalmol. Vis. Sci. 2015;56:983-992.
Not in our library10.1167/iovs.14-15859
50.
Bermudez M.A., Sendon-Lago J., Seoane S., Eiro N., Gonzalez F., Saa J., Vizoso F., Perez-Fernandez R. Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis. Exp. Eye Res. 2016;149:84-92.
Not in our library10.1016/j.exer.2016.06.022
51.
Osugi M., Katagiri W., Yoshimi R., Inukai T., Hibi H., Ueda M. Conditioned media from mesenchymal stem cells enhanced bone regeneration in rat calvarial bone defects. Tissue Eng. Part A. 2012;18:1479-1489.
Not in our library10.1089/ten.tea.2011.0325
52.
Vishnubhatla I., Corteling R., Stevanato L., Hicks C., Sinden J. The development of stem cell-derived exosomes as a cell-free regenerative medicine. J. Circ. Biomark. 2014;3:2.
Not in our library10.5772/58597
53.
Kim D.K., Nishida H., An S.Y., Shetty A.K., Bartosh T.J., Prockop D.J. Chromatographically isolated CD63+ CD81+ extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI. Proc. Natl. Acad. Sci. USA. 2016;113:170-175.
Not in our library10.1073/pnas.1522297113
54.
Justewicz D.M., Shokes J.E., Reavis B., Boyd S.A., Burnette T.B., Halberstadt C.R., Spencer T., Ludlow J.W., Bertram T.A., Jain D. Characterization of the human smooth muscle cell secretome for regenerative medicine. Tissue Eng. Part C Methods. 2012;18:797-816.
Not in our library10.1089/ten.tec.2012.0054
55.
Ionescu L., Byrne R.N., van Haaften T., Vadivel A., Alphonse R.S., Rey-Parra G.J., Weissmann G., Hall A., Eaton F., Thebaud B. Stem cell conditioned medium improves acute lung injury in mice: In vivo evidence for stem cell paracrine action. Am. J. Physiol. Lung Cell. Mol. Physiol. 2012;303:L967-L977.
Not in our library10.1152/ajplung.00144.2011
56.
Timmers L., Lim S.K., Arslan F., Armstrong J.S., Hoefer I.E., Doevendans P.A., Piek J.J., El Oakley R.M., Choo A., Lee C.N., et al. Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium. Stem Cell. Res. 2007;1:129-137.
Not in our library10.1016/j.scr.2008.02.002
57.
Chang C.P., Chio C.C., Cheong C.U., Chao C.M., Cheng B.C., Lin M.T. Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin. Sci. 2013;124:165-176.
Not in our library10.1042/cs20120226
58.
The Relative Contribution of Paracine Effect versus Direct Differentiation on Adipose-Derived Stem Cell Transplantation Mediated Cardiac Repair · 2013
No notice
59.
Sevivas N., Teixeira F.G., Portugal R., Araujo L., Carrico L.F., Ferreira N., Vieira da Silva M., Espregueira-Mendes J., Anjo S., Manadas B., et al. Mesenchymal stem cell secretome: A potential tool for the prevention of muscle degenerative changes associated with chronic rotator cuff tears. Am. J. Sports Med. 2016.
Not in our library10.1177/0363546516657827
60.
Bhang S.H., Lee S., Shin J.Y., Lee T.J., Jang H.K., Kim B.S. Efficacious and clinically relevant conditioned medium of human adipose-derived stem cells for therapeutic angiogenesis. Mol. Ther. 2014;22:862-872.
Not in our library10.1038/mt.2013.301
61.
Zhou B.R., Xu Y., Guo S.L., Wang Y., Zhu F., Permatasari F., Wu D., Yin Z.Q., Luo D. The effect of conditioned media of adipose-derived stem cells on wound healing after ablative fractional carbon dioxide laser resurfacing. BioMed Res. Int. 2013;2013:519126.
Not in our library10.1155/2013/519126
62.
Legaki E., Roubelakis M.G., Theodoropoulos G.E., Lazaris A., Kollia A., Karamanolis G., Marinos E., Gazouli M. Therapeutic potential of secreted molecules derived from human amniotic fluid mesenchymal stem/stroma cells in a mice model of colitis. Stem Cell Rev. 2016;12:604-612.
Not in our library10.1007/s12015-016-9677-1
63.
Zagoura D.S., Roubelakis M.G., Bitsika V., Trohatou O., Pappa K.I., Kapelouzou A., Antsaklis A., Anagnou N.P. Therapeutic potential of a distinct population of human amniotic fluid mesenchymal stem cells and their secreted molecules in mice with acute hepatic failure. Gut. 2012;61:894-906.
Not in our library10.1136/gutjnl-2011-300908
64.
Mita T., Furukawa-Hibi Y., Takeuchi H., Hattori H., Yamada K., Hibi H., Ueda M., Yamamoto A. Conditioned medium from the stem cells of human dental pulp improves cognitive function in a mouse model of Alzheimer’s disease. Behav. Brain Res. 2015;293:189-197.
Not in our library10.1016/j.bbr.2015.07.043
65.
Katagiri W., Watanabe J., Toyama N., Osugi M., Sakaguchi K., Hibi H. Clinical study of bone regeneration by conditioned medium from mesenchymal stem cells after maxillary sinus floor elevation. Implant. Dent. 2017;26:607-612.
Not in our library10.1097/id.0000000000000618
66.
Hassan Famian M., Montazer Saheb S., Montaseri A. Conditioned medium of Wharton’s jelly derived stem cells can enhance the cartilage specific genes expression by chondrocytes in monolayer and mass culture systems. Adv. Pharm. Bull. 2017;7:123-130.
Not in our library10.15171/apb.2017.016
67.
Park B.S., Kim W.S., Choi J.S., Kim H.K., Won J.H., Ohkubo F., Fukuoka H. Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: Evidence of increased growth factor secretion. Biomed. Res. 2010;31:27-34.
Not in our library10.2220/biomedres.31.27
68.
Jang Y.J., An S.Y., Kim J.H. Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis. BMB Rep. 2017;50:58-59.
Not in our library10.5483/bmbrep.2017.50.2.012
69.
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal Behavior in a Rat Model of Parkinson's Disease · 2016
No notice
70.
Rajan T.S., Giacoppo S., Diomede F., Ballerini P., Paolantonio M., Marchisio M., Piattelli A., Bramanti P., Mazzon E., Trubiani O. The secretome of periodontal ligament stem cells from MS patients protects against EAE. Sci. Rep. 2016;6:38743.
Not in our library10.1038/srep38743
71.
Kim M.J., Kim Z.H., Kim S.M., Choi Y.S. Conditioned medium derived from umbilical cord mesenchymal stem cells regenerates atrophied muscles. Tissue Cell. 2016;48:533-543.
Not in our library10.1016/j.tice.2016.06.010
72.
Keating A. Mesenchymal stromal cells: New directions. Cell Stem Cell. 2012;10:709-716.
Not in our library10.1016/j.stem.2012.05.015
73.
Fierabracci A., del Fattore A., Muraca M., Delfino D.V. The use of mesenchymal stem cells for the treatment of autoimmunity: From animals models to human disease. Curr. Drug Targets. 2016;17:229-238.
Not in our library10.2174/1389450116666150722140633
74.
Le Blanc K., Rasmusson I., Sundberg B., Gotherstrom C., Hassan M., Uzunel M., Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004;363:1439-1441.
Not in our library10.1016/s0140-6736(04)16104-7
75.
English K., French A., Wood K.J. Mesenchymal stromal cells: Facilitators of successful transplantation? Cell Stem Cell. 2010;7:431-442.
Not in our library10.1016/j.stem.2010.09.009
76.
Mesenchymal stem cells avoid allogeneic rejection · 2005
No notice
77.
Fierabracci A., del Fattore A., Muraca M. The immunoregulatory activity of mesenchymal stem cells: ‘State of art’ and ‘future avenues’. Curr. Med. Chem. 2016;23:3014-3024.
Not in our library10.2174/0929867323666160627112827
78.
Di Nicola M., Carlo-Stella C., Magni M., Milanesi M., Longoni P.D., Matteucci P., Grisanti S., Gianni A.M. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838-3843.
Not in our library10.1182/blood.v99.10.3838
79.
Liang X., Ding Y., Zhang Y., Tse H.F., Lian Q. Paracrine mechanisms of mesenchymal stem cell-based therapy: Current status and perspectives. Cell Transplant. 2014;23:1045-1059.
Not in our library10.3727/096368913x667709
80.
Conditioned Medium from Bone Marrow-Derived Mesenchymal Stem Cells Improves Recovery after Spinal Cord Injury in Rats: An Original Strategy to Avoid Cell Transplantation · 2013
No notice
81.
See F., Seki T., Psaltis P.J., Sondermeijer H.P., Gronthos S., Zannettino A.C., Govaert K.M., Schuster M.D., Kurlansky P.A., Kelly D.J., et al. Therapeutic effects of human STRO-3-selected mesenchymal precursor cells and their soluble factors in experimental myocardial ischemia. J. Cell. Mol. Med. 2011;15:2117-2129.
Not in our library10.1111/j.1582-4934.2010.01241.x
82.
Mirabella T., Cilli M., Carlone S., Cancedda R., Gentili C. Amniotic liquid derived stem cells as reservoir of secreted angiogenic factors capable of stimulating neo-arteriogenesis in an ischemic model. Biomaterials. 2011;32:3689-3699.
Not in our library10.1016/j.biomaterials.2011.01.071
83.
Lee M.J., Kim J., Lee K.I., Shin J.M., Chae J.I., Chung H.M. Enhancement of wound healing by secretory factors of endothelial precursor cells derived from human embryonic stem cells. Cytotherapy. 2011;13:165-178.
Not in our library10.3109/14653249.2010.512632
84.
Caplan A.I. Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J. Cell. Physiol. 2007;213:341-347.
Not in our library10.1002/jcp.21200
85.
Yi T., Song S.U. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch. Pharm. Res. 2012;35:213-221.
Not in our library10.1007/s12272-012-0202-z
86.
Li B., Zhang H., Zeng M., He W., Li M., Huang X., Deng D.Y., Wu J. Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide-induced apoptosis partially by inhibiting the Wnt/β-catenin pathway. Cell Biol. Int. 2015;39:192-200.
Not in our library10.1002/cbin.10359
87.
Tang Y.L., Zhao Q., Qin X., Shen L., Cheng L., Ge J., Phillips M.I. Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann. Thorac. Surg. 2005;80:229-236.
Not in our library10.1016/j.athoracsur.2005.02.072
88.
Ranganath S.H., Levy O., Inamdar M.S., Karp J.M. Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell. 2012;10:244-258.
Not in our library10.1016/j.stem.2012.02.005
89.
Salgado A.J., Reis R.L., Sousa N.J., Gimble J.M. Adipose tissue derived stem cells secretome: Soluble factors and their roles in regenerative medicine. Curr. Stem Cell Res. Ther. 2010;5:103-110.
Not in our library10.2174/157488810791268564
90.
Stastna M., van Eyk J.E. Investigating the secretome: Lessons about the cells that comprise the heart. Circ. Cardiovasc. Genet. 2012;5:o8-o18.
Not in our library10.1161/circgenetics.111.960187
91.
The stem cell secretome and its role in brain repair · 2013
No notice
92.
Wilson S.E., Mohan R.R., Ambrosio R., Hong J., Lee J. The corneal wound healing response: Cytokine-mediated interaction of the epithelium, stroma, and inflammatory cells. Prog. Retin. Eye Res. 2001;20:625-637.
Not in our library10.1016/s1350-9462(01)00008-8
93.
Lu P., Li L., Wu Y., Mukaida N., Zhang X. Essential contribution of CCL3 to alkali-induced corneal neovascularization by regulating vascular endothelial growth factor production by macrophages. Mol. Vis. 2008;14:1614-1622.
Not in our library
94.
Kim J., Lee J.H., Yeo S.M., Chung H.M., Chae J.I. Stem cell recruitment factors secreted from cord blood-derived stem cells that are not secreted from mature endothelial cells enhance wound healing. In Vitro Cell. Dev. Biol. Anim. 2014;50:146-154.
Not in our library10.1007/s11626-013-9687-0
95.
Litwack G. Human Biochemistry and Disease. 2008.
Not in our library
96.
Ray P., Devaux Y., Stolz D.B., Yarlagadda M., Watkins S.C., Lu Y., Chen L., Yang X.F., Ray A. Inducible expression of keratinocyte growth factor (KGF) in mice inhibits lung epithelial cell death induced by hyperoxia. Proc. Natl. Acad. Sci. USA. 2003;100:6098-6103.
Not in our library10.1073/pnas.1031851100
97.
Turner J.E., Morrison P.J., Wilhelm C., Wilson M., Ahlfors H., Renauld J.C., Panzer U., Helmby H., Stockinger B. IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation. J. Exp. Med. 2013;210:2951-2965.
Not in our library10.1084/jem.20130071
98.
Bakondi B., Shimada I.S., Perry A., Munoz J.R., Ylostalo J., Howard A.B., Gregory C.A., Spees J.L. CD133 identifies a human bone marrow stem/progenitor cell sub-population with a repertoire of secreted factors that protect against stroke. Mol. Ther. 2009;17:1938-1947.
Not in our library10.1038/mt.2009.185
99.
Cargnoni A., Ressel L., Rossi D., Poli A., Arienti D., Lombardi G., Parolini O. Conditioned medium from amniotic mesenchymal tissue cells reduces progression of bleomycin-induced lung fibrosis. Cytotherapy. 2012;14:153-161.
Not in our library10.3109/14653249.2011.613930
100.
Preda M.B., Ronningen T., Burlacu A., Simionescu M., Moskaug J.O., Valen G. Remote transplantation of mesenchymal stem cells protects the heart against ischemia-reperfusion injury. Stem Cells. 2014;32:2123-2134.
Not in our library10.1002/stem.1687
101.
Tang J., Wang J., Guo L., Kong X., Yang J., Zheng F., Zhang L., Huang Y. Mesenchymal stem cells modified with stromal cell-derived factor 1 α improve cardiac remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Mol. Cells. 2010;29:9-19.
Not in our library10.1007/s10059-010-0001-7
102.
Williams A.R., Suncion V.Y., McCall F., Guerra D., Mather J., Zambrano J.P., Heldman A.W., Hare J.M. Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling. J. Am. Heart Assoc. 2013;2:e000140.
Not in our library10.1161/jaha.113.000140
103.
Ratajczak J., Bronckaers A., Dillen Y., Gervois P., Vangansewinkel T., Driesen R.B., Wolfs E., Lambrichts I., Hilkens P. The neurovascular properties of dental stem cells and their importance in dental tissue engineering. Stem Cells Int. 2016;2016:9762871.
Not in our library10.1155/2016/9762871
104.
Caseiro A.R., Pereira T., Ivanova G., Luis A.L., Mauricio A.C. Neuromuscular regeneration: Perspective on the application of mesenchymal stem cells and their secretion products. Stem Cells Int. 2016;2016:9756973.
Not in our library10.1155/2016/9756973
105.
Luarte A., Batiz L.F., Wyneken U., Lafourcade C. Potential therapies by stem cell-derived exosomes in CNS diseases: Focusing on the neurogenic niche. Stem Cells Int. 2016;2016:5736059.
Not in our library10.1155/2016/5736059
106.
De Almeida J.F., Chen P., Henry M.A., Diogenes A. Stem cells of the apical papilla regulate trigeminal neurite outgrowth and targeting through a BDNF-dependent mechanism. Tissue Eng. Part A. 2014;20:3089-3100.
Not in our library10.1089/ten.tea.2013.0347
107.
Paracrine-Mediated Neuroprotection and Neuritogenesis of Axotomised Retinal Ganglion Cells by Human Dental Pulp Stem Cells: Comparison with Human Bone Marrow and Adipose-Derived Mesenchymal Stem Cells · 2014
No notice
108.
Salgado A.J., Sousa J.C., Costa B.M., Pires A.O., Mateus-Pinheiro A., Teixeira F.G., Pinto L., Sousa N. Mesenchymal stem cells secretome as a modulator of the neurogenic niche: Basic insights and therapeutic opportunities. Front. Cell Neurosci. 2015;9:249.
Not in our library10.3389/fncel.2015.00249
109.
Burlacu A., Grigorescu G., Rosca A.M., Preda M.B., Simionescu M. Factors secreted by mesenchymal stem cells and endothelial progenitor cells have complementary effects on angiogenesis in vitro. Stem Cells Dev. 2013;22:643-653.
Not in our library10.1089/scd.2012.0273
110.
Mesenchymal Stem Cells from Human Umbilical Cord Express Preferentially Secreted Factors Related to Neuroprotection, Neurogenesis, and Angiogenesis · 2013
No notice
111.
Liu G., Pareta R.A., Wu R., Shi Y., Zhou X., Liu H., Deng C., Sun X., Atala A., Opara E.C., et al. Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis using microbeads loaded with growth factors. Biomaterials. 2013;34:1311-1326.
Not in our library10.1016/j.biomaterials.2012.10.038
112.
Sharma A.K., Bury M.I., Fuller N.J., Marks A.J., Kollhoff D.M., Rao M.V., Hota P.V., Matoka D.J., Edassery S.L., Thaker H., et al. Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration. Proc. Natl. Acad. Sci. USA. 2013;110:4003-4008.
Not in our library10.1073/pnas.1220764110
113.
Mesenchymal Stem Cells Secrete Multiple Cytokines That Promote Angiogenesis and Have Contrasting Effects on Chemotaxis and Apoptosis · 2012
No notice
114.
Kinnaird T., Stabile E., Burnett M.S., Shou M., Lee C.W., Barr S., Fuchs S., Epstein S.E. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation. 2004;109:1543-1549.
Not in our library10.1161/01.cir.0000124062.31102.57
115.
Hung S.C., Pochampally R.R., Chen S.C., Hsu S.C., Prockop D.J. Angiogenic effects of human multipotent stromal cell conditioned medium activate the PI3K-Akt pathway in hypoxic endothelial cells to inhibit apoptosis, increase survival, and stimulate angiogenesis. Stem Cells. 2007;25:2363-2370.
Not in our library10.1634/stemcells.2006-0686
116.
Wu Y., Chen L., Scott P.G., Tredget E.E. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells. 2007;25:2648-2659.
Not in our library10.1634/stemcells.2007-0226
117.
Chen X., Lin X., Zhao J., Shi W., Zhang H., Wang Y., Kan B., Du L., Wang B., Wei Y., et al. A tumor-selective biotherapy with prolonged impact on established metastases based on cytokine gene-engineered MSCs. Mol. Ther. 2008;16:749-756.
Not in our library10.1038/mt.2008.3
118.
Estrada R., Li N., Sarojini H., An J., Lee M.J., Wang E. Secretome from mesenchymal stem cells induces angiogenesis via Cyr61. J. Cell. Physiol. 2009;219:563-571.
Not in our library10.1002/jcp.21701
119.
Novel Cell-Free Strategy for Therapeutic Angiogenesis: In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation · 2009
No notice
120.
Yun Y.R., Won J.E., Jeon E., Lee S., Kang W., Jo H., Jang J.H., Shin U.S., Kim H.W. Fibroblast growth factors: Biology, function, and application for tissue regeneration. J. Tissue Eng. 2010;2010:218142.
Not in our library10.4061/2010/218142
121.
Ho J.C., Lai W.H., Li M.F., Au K.W., Yip M.C., Wong N.L., Ng E.S., Lam F.F., Siu C.W., Tse H.F. Reversal of endothelial progenitor cell dysfunction in patients with type 2 diabetes using a conditioned medium of human embryonic stem cell-derived endothelial cells. Diabetes Metab. Res. Rev. 2012;28:462-473.
Not in our library10.1002/dmrr.2304
122.
Zanotti L., Angioni R., Cali B., Soldani C., Ploia C., Moalli F., Gargesha M., D’Amico G., Elliman S., Tedeschi G., et al. Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1. Leukemia. 2016;30:1143-1154.
Not in our library10.1038/leu.2016.33
123.
De Luca A., Gallo M., Aldinucci D., Ribatti D., Lamura L., D’Alessio A., De Filippi R., Pinto A., Normanno N. Role of the EGFR ligand/receptor system in the secretion of angiogenic factors in mesenchymal stem cells. J. Cell. Physiol. 2011;226:2131-2138.
Not in our library10.1002/jcp.22548
124.
Wong R.S. Mesenchymal stem cells: Angels or demons? J. Biomed. Biotechnol. 2011;2011:459510.
Not in our library10.1155/2011/459510
125.
The role of mesenchymal stem cells in anti-cancer drug resistance and tumour progression · 2012
No notice
126.
Attar-Schneider O., Zismanov V., Drucker L., Gottfried M. Secretome of human bone marrow mesenchymal stem cells: An emerging player in lung cancer progression and mechanisms of translation initiation. Tumor. Biol. 2016;37:4755-4765.
Not in our library10.1007/s13277-015-4304-3
127.
Marcus H., Attar-Schneider O., Dabbah M., Zismanov V., Tartakover-Matalon S., Lishner M., Drucker L. Mesenchymal stem cells secretomes’ affect multiple myeloma translation initiation. Cell. Signal. 2016;28:620-630.
Not in our library10.1016/j.cellsig.2016.03.003
128.
Onzi G.R., Ledur P.F., Hainzenreder L.D., Bertoni A.P., Silva A.O., Lenz G., Wink M.R. Analysis of the safety of mesenchymal stromal cells secretome for glioblastoma treatment. Cytotherapy. 2016;18:828-837.
Not in our library10.1016/j.jcyt.2016.03.299
129.
Karnoub A.E., Dash A.B., Vo A.P., Sullivan A., Brooks M.W., Bell G.W., Richardson A.L., Polyak K., Tubo R., Weinberg R.A. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449:557-563.
Not in our library10.1038/nature06188
130.
Muehlberg F.L., Song Y.H., Krohn A., Pinilla S.P., Droll L.H., Leng X., Seidensticker M., Ricke J., Altman A.M., Devarajan E., et al. Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis. 2009;30:589-597.
Not in our library10.1093/carcin/bgp036
131.
Galie M., Konstantinidou G., Peroni D., Scambi I., Marchini C., Lisi V., Krampera M., Magnani P., Merigo F., Montani M., et al. Mesenchymal stem cells share molecular signature with mesenchymal tumor cells and favor early tumor growth in syngeneic mice. Oncogene. 2008;27:2542-2551.
Not in our library10.1038/sj.onc.1210920
132.
Masuda H., Zhang D., Bartholomeusz C., Doihara H., Hortobagyi G.N., Ueno N.T. Role of epidermal growth factor receptor in breast cancer. Breast Cancer Res. Treat. 2012;136:331-345.
Not in our library10.1007/s10549-012-2289-9
133.
Korkaya H., Liu S., Wicha M.S. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J. Clin. Investig. 2011;121:3804-3809.
Not in our library10.1172/jci57099
134.
Park J.K., Park S.H., So K., Bae I.H., Yoo Y.D., Um H.D. ICAM-3 enhances the migratory and invasive potential of human non-small cell lung cancer cells by inducing MMP-2 and MMP-9 via Akt and CREB. Int. J. Oncol. 2010;36:181-192.
Not in our library10.3892/ijo_00000489
135.
Dethlefsen C., Hojfeldt G., Hojman P. The role of intratumoral and systemic IL-6 in breast cancer. Breast Cancer Res. Treat. 2013;138:657-664.
Not in our library10.1007/s10549-013-2488-z
136.
Won H.S., Kim Y.A., Lee J.S., Jeon E.K., An H.J., Sun D.S., Ko Y.H., Kim J.S. Soluble interleukin-6 receptor is a prognostic marker for relapse-free survival in estrogen receptor-positive breast cancer. Cancer Investig. 2013;31:516-521.
Not in our library10.3109/07357907.2013.826239
137.
Rajaram M., Li J., Egeblad M., Powers R.S. System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity. PLoS Genet. 2013;9:e1003789.
Not in our library10.1371/journal.pgen.1003789
138.
Dual role of macrophage migration inhibitory factor (MIF) in human breast cancer · 2009
No notice
139.
Karnezis T., Shayan R., Caesar C., Roufail S., Harris N.C., Ardipradja K., Zhang Y.F., Williams S.P., Farnsworth R.H., Chai M.G., et al. VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. Cancer Cell. 2012;21:181-195.
Not in our library10.1016/j.ccr.2011.12.026
140.
Pasero C., Barbarat B., Just-Landi S., Bernard A., Aurran-Schleinitz T., Rey J., Eldering E., Truneh A., Costello R.T., Olive D. A role for HVEM, but not lymphotoxin-β receptor, in LIGHT-induced tumor cell death and chemokine production. Eur. J. Immunol. 2009;39:2502-2514.
Not in our library10.1002/eji.200939069
141.
Silver D.F., Hempling R.E., Piver M.S., Repasky E.A. Flt-3 ligand inhibits growth of human ovarian tumors engrafted in severe combined immunodeficient mice. Gynecol. Oncol. 2000;77:377-382.
Not in our library10.1006/gyno.2000.5782
142.
Bronger H., Kraeft S., Schwarz-Boeger U., Cerny C., Stockel A., Avril S., Kiechle M., Schmitt M. Modulation of CXCR3 ligand secretion by prostaglandin E2 and cyclooxygenase inhibitors in human breast cancer. Breast Cancer Res. 2012;14:R30.
Not in our library10.1186/bcr3115
143.
Schneider J., Eiro N., Perez-Fernandez R., Martinez-Ordonez A., Vizoso F. Human uterine cervical stromal stem cells (hUCESCs): Why and how they exert their antitumor activity. Cancer Genom. Proteom. 2016;13:331-337.
Not in our library
144.
Grizzle W.E., Srivastava S., Manne U. The biology of incipient, pre-invasive or intraepithelial neoplasia. Cancer Biomark. 2010;9:21-39.
Not in our library10.3233/cbm-2011-0172
145.
Bhowmick N.A., Neilson E.G., Moses H.L. Stromal fibroblasts in cancer initiation and progression. Nature. 2004;432:332-337.
Not in our library10.1038/nature03096
146.
Study of matrix metalloproteinases and their inhibitors in breast cancer · 2007
No notice
147.
Mao Y., Keller E.T., Garfield D.H., Shen K., Wang J. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 2013;32:303-315.
Not in our library10.1007/s10555-012-9415-3
148.
Allavena P., Sica A., Solinas G., Porta C., Mantovani A. The inflammatory micro-environment in tumor progression: The role of tumor-associated macrophages. Crit. Rev. Oncol. Hematol. 2008;66:1-9.
Not in our library10.1016/j.critrevonc.2007.07.004
149.
Becker J.C., Andersen M.H., Schrama D., Thor Straten P. Immune-suppressive properties of the tumor microenvironment. Cancer Immunol. Immunother. 2013;62:1137-1148.
Not in our library10.1007/s00262-013-1434-6
150.
Prognostic Significance of Tumor-Associated Macrophages in Solid Tumor: A Meta-Analysis of the Literature · 2012
No notice
151.
Eiro N., Pidal I., Fernandez-Garcia B., Junquera S., Lamelas M.L., del Casar J.M., Gonzalez L.O., Lopez-Muniz A., Vizoso F.J. Impact of CD68/(CD3+ CD20) ratio at the invasive front of primary tumors on distant metastasis development in breast cancer. PLoS ONE. 2012;7:e52796.
Not in our library10.1371/journal.pone.0052796
152.
Gupta N., Su X., Popov B., Lee J.W., Serikov V., Matthay M.A. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J. Immunol. 2007;179:1855-1863.
Not in our library10.4049/jimmunol.179.3.1855
153.
Gonzalez-Rey E., Anderson P., Gonzalez M.A., Rico L., Buscher D., Delgado M. Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut. 2009;58:929-939.
Not in our library10.1136/gut.2008.168534
154.
Nemeth K., Leelahavanichkul A., Yuen P.S., Mayer B., Parmelee A., Doi K., Robey P.G., Leelahavanichkul K., Koller B.H., Brown J.M., et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat. Med. 2009;15:42-49.
Not in our library10.1038/nm.1905
155.
Mei S.H., Haitsma J.J., Dos Santos C.C., Deng Y., Lai P.F., Slutsky A.S., Liles W.C., Stewart D.J. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am. J. Respir. Crit. Care Med. 2010;182:1047-1057.
Not in our library10.1164/rccm.201001-0010oc
156.
Krasnodembskaya A., Song Y., Fang X., Gupta N., Serikov V., Lee J.W., Matthay M.A. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide IL-37. Stem Cells. 2010;28:2229-2238.
Not in our library10.1002/stem.544
157.
Yang D., Chen Q., Hoover D.M., Staley P., Tucker K.D., Lubkowski J., Oppenheim J.J. Many chemokines including CCL20/MIP-3α display antimicrobial activity. J. Leukoc. Biol. 2003;74:448-455.
Not in our library10.1189/jlb.0103024
158.
Egesten A., Eliasson M., Johansson H.M., Olin A.I., Morgelin M., Mueller A., Pease J.E., Frick I.M., Bjorck L. The CXC chemokine MIG/CXCl9 is important in innate immunity against streptococcus pyogenes. J. Infect. Dis. 2007;195:684-693.
Not in our library10.1086/510857
159.
Yount N.Y., Waring A.J., Gank K.D., Welch W.H., Kupferwasser D., Yeaman M.R. Structural correlates of antimicrobial efficacy in IL-8 and related human kinocidins. Biochim. Biophys. Acta. 2007;1768:598-608.
Not in our library10.1016/j.bbamem.2006.11.011
160.
Collin M., Linge H.M., Bjartell A., Giwercman A., Malm J., Egesten A. Constitutive expression of the antibacterial CXC chemokine GCP-2/CXCL6 by epithelial cells of the male reproductive tract. J. Reprod. Immunol. 2008;79:37-43.
Not in our library10.1016/j.jri.2008.08.003
161.
Linge H.M., Collin M., Nordenfelt P., Morgelin M., Malmsten M., Egesten A. The human CXC chemokine granulocyte chemotactic protein 2 (GCP-2)/CXCL6 possesses membrane-disrupting properties and is antibacterial. Antimicrob. Agents Chemother. 2008;52:2599-2607.
Not in our library10.1128/aac.00028-08
162.
Vieira N.M., Zucconi E., Bueno C.R., Secco M., Suzuki M.F., Bartolini P., Vainzof M., Zatz M. Human multipotent mesenchymal stromal cells from distinct sources show different in vivo potential to differentiate into muscle cells when injected in dystrophic mice. Stem Cell Rev. 2010;6:560-566.
Not in our library10.1007/s12015-010-9187-5
163.
Assoni A., Castello G., Valadares M., Beccari M., Gomes J., Pelatti M., Mitne-Neto M., Carvalho V.M., Zatz M. Different donors mesenchymal stromal cells secretomes reveal heterogeneous profile of relevance for therapeutic use. Stem Cells Dev. 2017;26:206-214.
Not in our library10.1089/scd.2016.0218
164.
Nakanishi C., Nagaya N., Ohnishi S., Yamahara K., Takabatake S., Konno T., Hayashi K., Kawashiri M.A., Tsubokawa T., Yamagishi M. Gene and protein expression analysis of mesenchymal stem cells derived from rat adipose tissue and bone marrow. Circ. J. 2011;75:2260-2268.
Not in our library10.1253/circj.cj-11-0246
165.
Pires A.O., Mendes-Pinheiro B., Teixeira F.G., Anjo S.I., Ribeiro-Samy S., Gomes E.D., Serra S.C., Silva N.A., Manadas B., Sousa N., et al. Unveiling the differences of secretome of human bone marrow mesenchymal stem cells, adipose tissue-derived stem cells, and human umbilical cord perivascular cells: A proteomic analysis. Stem Cells Dev. 2016;25:1073-1083.
Not in our library10.1089/scd.2016.0048
166.
Prospect of Stem Cell Conditioned Medium in Regenerative Medicine · 2014
No notice
167.
Basu J., Ludlow J.W. Exosomes for repair, regeneration and rejuvenation. Expert Opin. Biol. Ther. 2016;16:489-506.
Not in our library10.1517/14712598.2016.1131976
168.
Feng D., Zhao W.L., Ye Y.Y., Bai X.C., Liu R.Q., Chang L.F., Zhou Q., Sui S.F. Cellular internalization of exosomes occurs through phagocytosis. Traffic. 2010;11:675-687.
Not in our library10.1111/j.1600-0854.2010.01041.x
169.
Exosome Uptake Depends on ERK1/2-Heat Shock Protein 27 Signaling and Lipid Raft-mediated Endocytosis Negatively Regulated by Caveolin-1 · 2013
No notice
170.
Lee Y., El Andaloussi S., Wood M.J. Exosomes and microvesicles: Extracellular vesicles for genetic information transfer and gene therapy. Hum. Mol. Genet. 2012;21:R125-R134.
Not in our library10.1093/hmg/dds317
171.
Lamichhane T.N., Sokic S., Schardt J.S., Raiker R.S., Lin J.W., Jay S.M. Emerging roles for extracellular vesicles in tissue engineering and regenerative medicine. Tissue Eng. Part B Rev. 2015;21:45-54.
Not in our library10.1089/ten.teb.2014.0300
172.
Gyorgy B., Hung M.E., Breakefield X.O., Leonard J.N. Therapeutic applications of extracellular vesicles: Clinical promise and open questions. Annu. Rev. Pharmacol. Toxicol. 2015;55:439-464.
Not in our library10.1146/annurev-pharmtox-010814-124630
173.
Extracellular membrane vesicles from umbilical cord blood‐derived MSC protect against ischemic acute kidney injury, a feature that is lost after inflammatory conditioning · 2013
No notice
174.
Lai R.C., Arslan F., Lee M.M., Sze N.S., Choo A., Chen T.S., Salto-Tellez M., Timmers L., Lee C.N., El Oakley R.M., et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010;4:214-222.
Not in our library10.1016/j.scr.2009.12.003
175.
Gatti S., Bruno S., Deregibus M.C., Sordi A., Cantaluppi V., Tetta C., Camussi G. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol. Dial. Transplant. 2011;26:1474-1483.
Not in our library10.1093/ndt/gfr015
176.
Tang X.-D., Shi L., Monsel A., Li X.-Y., Zhu H.-L., Zhu Y.-G., Qu J.-M. Mesenchymal stem cell microvesicles attenuate acute lung injury in mice partly mediated by Ang-1 mRNA. Stem Cells. 2017;35:1849-1859.
Not in our library10.1002/stem.2619
177.
Zhang B., Shi Y., Gong A., Pan Z., Shi H., Yang H., Fu H., Yan Y., Zhang X., Wang M., et al. HucMSC exosome-delivered 14-3-3ζ orchestrates self-control of the Wnt response via modulation of YAP during cutaneous regeneration. Stem Cells. 2016;34:2485-2500.
Not in our library10.1002/stem.2432
178.
Yin G., Hu G., Wan R., Yu G., Cang X., Xiong J., Ni J., Hu Y., Xing M., Fan Y., et al. Role of microvesicles from bone marrow mesenchymal stem cells in acute pancreatitis. Pancreas. 2016;45:1282-1293.
Not in our library10.1097/mpa.0000000000000694
179.
Li T., Yan Y., Wang B., Qian H., Zhang X., Shen L., Wang M., Zhou Y., Zhu W., Li W., et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev. 2013;22:845-854.
Not in our library10.1089/scd.2012.0395
180.
Exosomes derived from miR‐181‐5p‐modified adipose‐derived mesenchymal stem cells prevent liver fibrosis via autophagy activation · 2017
No notice
181.
Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models · 2014
No notice
182.
Zhang B., Yin Y., Lai R.C., Tan S.S., Choo A.B., Lim S.K. Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev. 2014;23:1233-1244.
Not in our library10.1089/scd.2013.0479
183.
Exosomes Derived from Mesenchymal Stem Cells Suppress Angiogenesis by Down-Regulating VEGF Expression in Breast Cancer Cells · 2013
No notice
184.
Ono M., Kosaka N., Tominaga N., Yoshioka Y., Takeshita F., Takahashi R.U., Yoshida M., Tsuda H., Tamura K., Ochiya T. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci. Signal. 2014;7:ra63.
Not in our library10.1126/scisignal.2005231
185.
Liu S., Liu D., Chen C., Hamamura K., Moshaverinia A., Yang R., Liu Y., Jin Y., Shi S. MSC transplantation improves osteopenia via epigenetic regulation of notch signaling in lupus. Cell Metab. 2015;22:606-618.
Not in our library10.1016/j.cmet.2015.08.018
186.
Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis · 2017
Corrected
187.
Cui X., He Z., Liang Z., Chen Z., Wang H., Zhang J. Exosomes from adipose-derived mesenchymal stem cells protect ischemic myocardium from ischemia/reperfusion injury via Wnt/[β]-catenin signaling pathway. J. Cardiovasc. Pharmacol. 2017.
Not in our library10.1097/fjc.0000000000000507
188.
Long Q., Upadhya D., Hattiangady B., Kim D.-K., An S.Y., Shuai B., Prockop D.J., Shetty A.K. Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus. Proc. Natl. Acad. Sci. USA. 2017;114:E3536-E3545.
Not in our library10.1073/pnas.1703920114
189.
Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis · 2017
No notice
190.
Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell–derived Exosomes to Glioblastoma Multiforme Cells Conferred Chemosensitivity · 2013
Not checked
191.
Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma · 2015
No notice
192.
Microvesicles Derived from Human Umbilical Cord Wharton’s Jelly Mesenchymal Stem Cells Attenuate Bladder Tumor Cell Growth In Vitro and In Vivo · 2013
No notice
193.
Bruno S., Collino F., Deregibus M.C., Grange C., Tetta C., Camussi G. Microvesicles derived from human bone marrow mesenchymal stem cells inhibit tumor growth. Stem Cells Dev. 2013;22:758-771.
Not in our library10.1089/scd.2012.0304
194.
Human Liver Stem Cell-Derived Microvesicles Inhibit Hepatoma Growth in SCID Mice by Delivering Antitumor MicroRNAs · 2012
No notice
195.
Altanerova U., Benejova K., Altanerova V., Tyciakova S., Rychly B., Szomolanyi P., Ciampor F., Cihova M., Repiska V., Ondicova K., et al. Dental pulp mesenchymal stem/stromal cells labeled with iron sucrose release exosomes and cells applied intra-nasally migrate to intracerebral glioblastoma. Neoplasma. 2016;63:925-933.
Not in our library10.4149/neo_2016_611
196.
Altaner C. Prodrug gene therapy for cancer mediated by mesenchymal stem/stromal cells engineered to express yeast cytosinedeaminase::Uracilphos phoribosyltransferase. J. Stem Cell Res. Ther. 2015;5:264.
Not in our library
197.
Santangelo L., Giurato G., Cicchini C., Montaldo C., Mancone C., Tarallo R., Battistelli C., Alonzi T., Weisz A., Tripodi M. The RNA-binding protein SYNCRIP is a component of the hepatocyte exosomal machinery controlling microRNA sorting. Cell. Rep. 2016;17:799-808.
Not in our library10.1016/j.celrep.2016.09.031
198.
Didiot M.C., Hall L.M., Coles A.H., Haraszti R.A., Godinho B.M., Chase K., Sapp E., Ly S., Alterman J.F., Hassler M.R., et al. Exosome-mediated delivery of hydrophobically modified siRNA for huntingtin mRNA silencing. Mol. Ther. 2016;24:1836-1847.
Not in our library10.1038/mt.2016.126
199.
Valadi H., Ekstrom K., Bossios A., Sjostrand M., Lee J.J., Lotvall J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007;9:654-659.
Not in our library10.1038/ncb1596
200.
Stenqvist A.C., Nagaeva O., Baranov V., Mincheva-Nilsson L. Exosomes secreted by human placenta carry functional Fas ligand and TRAIL molecules and convey apoptosis in activated immune cells, suggesting exosome-mediated immune privilege of the fetus. J. Immunol. 2013;191:5515-5523.
Not in our library10.4049/jimmunol.1301885
201.
Lai C.P., Mardini O., Ericsson M., Prabhakar S., Maguire C.A., Chen J.W., Tannous B.A., Breakefield X.O. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano. 2014;8:483-494.
Not in our library10.1021/nn404945r
202.
Santangelo L., Battistelli C., Montaldo C., Citarella F., Strippoli R., Cicchini C. Functional roles and therapeutic applications of exosomes in hepatocellular carcinoma. Biomed. Res. Int. 2017;2017:2931813.
Not in our library10.1155/2017/2931813
203.
Katsuda T., Tsuchiya R., Kosaka N., Yoshioka Y., Takagaki K., Oki K., Takeshita F., Sakai Y., Kuroda M., Ochiya T. Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes. Sci. Rep. 2013;3:1197.
Not in our library10.1038/srep01197
204.
Lee M., Liu T., Im W., Kim M. Exosomes from adipose-derived stem cells ameliorate phenotype of Huntington’s disease in vitro model. Eur. J. Neurosci. 2016;44:2114-2119.
Not in our library10.1111/ejn.13275
205.
Lopez-Verrilli M.A., Caviedes A., Cabrera A., Sandoval S., Wyneken U., Khoury M. Mesenchymal stem cell-derived exosomes from different sources selectively promote neuritic outgrowth. Neuroscience. 2016;320:129-139.
Not in our library10.1016/j.neuroscience.2016.01.061
206.
MSCs-Derived Exosomes: Cell-Secreted Nanovesicles with Regenerative Potential · 2016
No notice
207.
Fukuoka H., Suga H. Hair regeneration treatment using adipose-derived stem cell conditioned medium: Follow-up with trichograms. Eplasty. 2015;15:e10.
Not in our library
208.
Shin H., Ryu H.H., Kwon O., Park B.S., Jo S.J. Clinical use of conditioned media of adipose tissue-derived stem cells in female pattern hair loss: A retrospective case series study. Int. J. Dermatol. 2015;54:730-735.
Not in our library10.1111/ijd.12650
209.
Katagiri W., Osugi M., Kawai T., Hibi H. First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells. Head Face Med. 2016;12:5.
Not in our library10.1186/s13005-016-0101-5
210.
Kordelas L., Rebmann V., Ludwig A.K., Radtke S., Ruesing J., Doeppner T.R., Epple M., Horn P.A., Beelen D.W., Giebel B. MSC-derived exosomes: A novel tool to treat therapy-refractory graft-versus-host disease. Leukemia. 2014;28:970-973.
Not in our library10.1038/leu.2014.41
211.
Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs · 2011
No notice
212.
Ahluwalia A., Tarnawski A.S. Critical role of hypoxia sensor-HIF-1α in VEGF gene activation. Implications for angiogenesis and tissue injury healing. Curr. Med. Chem. 2012;19:90-97.
Not in our library10.2174/092986712803413944
213.
Hawkins K.E., Sharp T.V., McKay T.R. The role of hypoxia in stem cell potency and differentiation. Regen. Med. 2013;8:771-782.
Not in our library10.2217/rme.13.71
214.
Youn S.W., Lee S.W., Lee J., Jeong H.K., Suh J.W., Yoon C.H., Kang H.J., Kim H.Z., Koh G.Y., Oh B.H., et al. Comp-Ang1 stimulates HIF-1α-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment. Blood. 2011;117:4376-4386.
Not in our library10.1182/blood-2010-07-295964
215.
Hypoxic Culture Conditions as a Solution for Mesenchymal Stem Cell Based Regenerative Therapy · 2013
No notice
216.
Estrada J.C., Albo C., Benguria A., Dopazo A., Lopez-Romero P., Carrera-Quintanar L., Roche E., Clemente E.P., Enriquez J.A., Bernad A., et al. Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis. Cell Death Differ. 2012;19:743-755.
Not in our library10.1038/cdd.2011.172
217.
Fehrer C., Brunauer R., Laschober G., Unterluggauer H., Reitinger S., Kloss F., Gully C., Gassner R., Lepperdinger G. Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan. Aging Cell. 2007;6:745-757.
Not in our library10.1111/j.1474-9726.2007.00336.x
218.
Pattappa G., Thorpe S.D., Jegard N.C., Heywood H.K., de Bruijn J.D., Lee D.A. Continuous and uninterrupted oxygen tension influences the colony formation and oxidative metabolism of human mesenchymal stem cells. Tissue Eng. Part C Methods. 2013;19:68-79.
Not in our library10.1089/ten.tec.2011.0734
219.
D’Ippolito G., Diabira S., Howard G.A., Roos B.A., Schiller P.C. Low oxygen tension inhibits osteogenic differentiation and enhances stemness of human miami cells. Bone. 2006;39:513-522.
Not in our library10.1016/j.bone.2006.02.061
220.
Yamamoto Y., Fujita M., Tanaka Y., Kojima I., Kanatani Y., Ishihara M., Tachibana S. Low oxygen tension enhances proliferation and maintains stemness of adipose tissue-derived stromal cells. Biores. Open Access. 2013;2:199-205.
Not in our library10.1089/biores.2013.0004
221.
Liu L., Gao J., Yuan Y., Chang Q., Liao Y., Lu F. Hypoxia preconditioned human adipose derived mesenchymal stem cells enhance angiogenic potential via secretion of increased VEGF and BFGF. Cell Biol. Int. 2013;37:551-560.
Not in our library10.1002/cbin.10097
222.
Ahmed N.E., Murakami M., Kaneko S., Nakashima M. The effects of hypoxia on the stemness properties of human dental pulp stem cells (DPSCs). Sci. Rep. 2016;6:35476.
Not in our library10.1038/srep35476
223.
Hypoxic Conditioned Medium From Human Adipose‐Derived Stem Cells Promotes Mouse Liver Regeneration Through JAK/STAT3 Signaling · 2016
Not checked
224.
Yu J., Yin S., Zhang W., Gao F., Liu Y., Chen Z., Zhang M., He J., Zheng S. Hypoxia preconditioned bone marrow mesenchymal stem cells promote liver regeneration in a rat massive hepatectomy model. Stem Cell Res. Ther. 2013;4:83.
Not in our library10.1186/scrt234
225.
Interferon-γ Regulates the Proliferation and Differentiation of Mesenchymal Stem Cells via Activation of Indoleamine 2,3 Dioxygenase (IDO) · 2011
No notice
226.
Kang J.W., Koo H.C., Hwang S.Y., Kang S.K., Ra J.C., Lee M.H., Park Y.H. Immunomodulatory effects of human amniotic membrane-derived mesenchymal stem cells. J. Vet. Sci. 2012;13:23-31.
Not in our library10.4142/jvs.2012.13.1.23
227.
Lin W., Oh S.K., Choo A.B., George A.J. Activated T cells modulate immunosuppression by embryonic-and bone marrow-derived mesenchymal stromal cells through a feedback mechanism. Cytotherapy. 2012;14:274-284.
Not in our library10.3109/14653249.2011.635853
228.
Kwon Y.W., Heo S.C., Jeong G.O., Yoon J.W., Mo W.M., Lee M.J., Jang I.H., Kwon S.M., Lee J.S., Kim J.H. Tumor necrosis factor-α-activated mesenchymal stem cells promote endothelial progenitor cell homing and angiogenesis. Biochim. Biophys. Acta. 2013;1832:2136-2144.
Not in our library10.1016/j.bbadis.2013.08.002
229.
Lu Z., Wang G., Dunstan C.R., Chen Y., Lu W.Y., Davies B., Zreiqat H. Activation and promotion of adipose stem cells by tumour necrosis factor-α preconditioning for bone regeneration. J. Cell Physiol. 2013;228:1737-1744.
Not in our library10.1002/jcp.24330
230.
Grote K., Petri M., Liu C., Jehn P., Spalthoff S., Kokemuller H., Luchtefeld M., Tschernig T., Krettek C., Haasper C., et al. Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes angiogenesis by paracrine factors. Eur. Cell Mater. 2013;26:66-79.
Not in our library10.22203/ecm.v026a05
231.
Cho Y.J., Song H.S., Bhang S., Lee S., Kang B.G., Lee J.C., An J., Cha C.I., Nam D.H., Kim B.S., et al. Therapeutic effects of human adipose stem cell-conditioned medium on stroke. J. Neurosci. Res. 2012;90:1794-1802.
Not in our library10.1002/jnr.23063
232.
Ma T., Grayson W.L., Frohlich M., Vunjak-Novakovic G. Hypoxia and stem cell-based engineering of mesenchymal tissues. Biotechnol. Prog. 2009;25:32-42.
Not in our library10.1002/btpr.128
233.
Bartosh T.J., Ylostalo J.H., Mohammadipoor A., Bazhanov N., Coble K., Claypool K., Lee R.H., Choi H., Prockop D.J. Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proc. Natl. Acad. Sci. USA. 2010;107:13724-13729.
Not in our library10.1073/pnas.1008117107
234.
Frith J.E., Thomson B., Genever P.G. Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Eng. Part C Methods. 2010;16:735-749.
Not in our library10.1089/ten.tec.2009.0432
235.
Ranganath S.H., Tong Z., Levy O., Martyn K., Karp J.M., Inamdar M.S. Controlled inhibition of the mesenchymal stromal cell pro-inflammatory secretome via microparticle engineerifng. Stem Cell Rep. 2016;6:926-939.
Not in our library10.1016/j.stemcr.2016.05.003

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Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration · 2023
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Mesenchymal stem cells: A new therapeutic tool for chronic kidney disease · 2022
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Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review · 2022
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Therapeutic Properties of Mesenchymal Stromal/Stem Cells: The Need of Cell Priming for Cell-Free Therapies in Regenerative Medicine · 2021
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CM from intact hAM: an easily obtained product with relevant implications for translation in regenerative medicine · 2021
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Comparative Proteomic Analysis of the Mesenchymal Stem Cells Secretome from Adipose, Bone Marrow, Placenta and Wharton’s Jelly · 2021
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Mesenchymal Stem Cell-Macrophage Crosstalk and Maintenance of Inflammatory Microenvironment Homeostasis · 2021
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Prospect of stem cells conditioned medium (secretome) in ligament and tendon healing: A systematic review · 2020
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Extracellular microvesicles/exosomes: discovery, disbelief, acceptance, and the future? · 2020
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Mesenchymal Stem Cell Secretome as an Emerging Cell-Free Alternative for Improving Wound Repair · 2020
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Therapeutic applications of adipose cell-free derivatives: a review · 2020
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Extracellular vesicles derived from human Wharton’s jelly mesenchymal stem cells protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers · 2019
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Fibroblast growth factor-2 stimulates proliferation of human adipose-derived stem cells via Src activation · 2019
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Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy · 2019
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Recent advances and challenges in the recovery and purification of cellular exosomes · 2019
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