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Enzymatic and non-enzymatic isolation systems for adipose tissue-derived cells: current state of the art

Eleni Oberbauer, Carolin Steffenhagen, Christoph Wurzer and 3 more

Cell Regeneration · 2015 · CC BY-NC-ND

doi:10.1186/s13619-015-0020-0

Abstract

In the past decade, adipose tissue became a highly interesting source of adult stem cells for plastic surgery and regenerative medicine. The isolated stromal vascular fraction (SVF) is a heterogeneous cell population including the adipose-derived stromal/stem cells (ASC), which showed regenerative potential in several clinical studies and trials. SVF should be provided in a safe and reproducible manner in accordance with current good manufacturing practices (cGMP). To ensure highest possible safety for patients, a precisely defined procedure with a high-quality control is required. Hence, an increasing number of adipose tissue-derived cell isolation systems have been developed. These systems aim for a closed, sterile, and safe isolation process limiting donor variations, risk for contaminations, and unpredictability of the cell material. To isolate SVF from adipose tissue, enzymes such as collagenase are used. Alternatively, in order to avoid enzymes, isolation systems using physical forces are available. Here, we provide an overview of known existing enzymatic and non-enzymatic adipose tissue-derived cell isolation systems, which are patented, published, or already on the market.

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    Stadler G, Hennerbichler S, Lindenmair A, Peterbauer A, Hofer K, van Griensven M, et al. Phenotypic shift of human amniotic epithelial cells in culture is associated with reduced osteogenic differentiation in vitro. Cytotherapy. 2008;10(7):743-52.

    Not in our library10.1080/14653240802345804

  95. 95.

    Kakagia D, Pallua N. Autologous fat grafting: in search of the optimal technique. Surg Innov. 2014;21(3):327-36.

    Not in our library10.1177/1553350613518846

  96. 96.

    Garza RM, Paik KJ, Chung MT, Duscher D, Gurtner GC, Longaker MT, et al. Studies in fat grafting: part III. Fat grafting irradiated tissue—improved skin quality and decreased fat graft retention. Plast Reconstr Surg. 2014;134(2):249-57.

    Not in our library10.1097/prs.0000000000000326

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    Stillaert FB, Di Bartolo C, Hunt JA, Rhodes NP, Tognana E, Monstrey S, et al. Human clinical experience with adipose precursor cells seeded on hyaluronic acid-based spongy scaffolds. Biomaterials. 2008;29(29):3953-9.

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    Matsumoto D, Sato K, Gonda K, Takaki Y, Shigeura T, Sato T, et al. Cell-assisted lipotransfer: supportive use of human adipose-derived cells for soft tissue augmentation with lipoinjection. Tissue Eng. 2006;12(12):3375-82.

    Not in our library10.1089/ten.2006.12.3375

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    Holnthoner W, Hohenegger K, Husa AM, Muehleder S, Meinl A, Peterbauer-Scherb A, et al. Adipose-derived stem cells induce vascular tube formation of outgrowth endothelial cells in a fibrin matrix. J Tissue Eng Regen Med. 2015;9(2):127-36.

    Not in our library10.1002/term.1620

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    Gentile P, Orlandi A, Scioli MG, Di Pasquali C, Bocchini I, Curcio CB, et al. A comparative translational study: the combined use of enhanced stromal vascular fraction and platelet-rich plasma improves fat grafting maintenance in breast reconstruction. Stem Cells Transl Med. 2012;1(4):341-51.

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    Jiang A, Li M, Duan W, Dong Y, Wang Y. Improvement of the survival of human autologous fat transplantation by adipose-derived stem-cells-assisted lipotransfer combined with bFGF. TheScientificWorldJOURNAL. 2015;2015:968057.

    Not in our library10.1155/2015/968057

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    Luo S, Hao L, Li X, Yu D, Diao Z, Ren L, et al. Adipose tissue-derived stem cells treated with estradiol enhance survival of autologous fat transplants. Tohoku J Exp Med. 2013;231(2):101-10.

    Not in our library10.1620/tjem.231.101

  103. 103.

    Li L, Pan S, Ni B, Lin Y. Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres. Cell Biol Int. 2014;38(8):962-70.

    Not in our library10.1002/cbin.10284

  104. 104.

    Van Pham P, Hong-Thien Bui K, Quoc Ngo D, Tan Khuat L, Kim PN. Transplantation of nonexpanded adipose stromal vascular fraction and platelet-rich plasma for articular cartilage injury treatment in mice model. J Med Eng. 2013;2013:7.

    Not in our library10.1155/2013/832396

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    Paspaliaris B, Thornton JAF. Methods and apparatuses for isolating and preparing stem cells. 2014.

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    Tzouvelekis A, Koliakos G, Ntolios P, Baira I, Bouros E, Oikonomou A, et al. Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal. J Transl Med. 2011;9:182.

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    Aronowitz JA, Ellenhorn JD. Adipose stromal vascular fraction isolation: a head-to-head comparison of four commercial cell separation systems. Plast Reconstr Surg. 2013;132(6):932e-9.

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  109. 109.

    Kakudo N, Tanaka Y, Morimoto N, Ogawa T, Kushida S, Hara T, et al. Adipose-derived regenerative cell (ADRC)-enriched fat grafting: optimal cell concentration and effects on grafted fat characteristics. J Transl Med. 2013;11:254.

    Not in our library10.1186/1479-5876-11-254

  110. 110.

    Granel B, Daumas A, Jouve E, Harle JR, Nguyen PS, Chabannon C, et al. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial. Ann Rheum Dis. 2014.

    Not in our library10.1136/annrheumdis-2014-205681

  111. 111.

    Gotoh M, Yamamoto T, Kato M, Majima T, Toriyama K, Kamei Y, et al. Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients. Int J Urol. 2014;21(3):294-300.

    Not in our library10.1111/iju.12266

  112. 112.

    Perez-Cano R, Vranckx JJ, Lasso JM, Calabrese C, Merck B, Milstein AM, et al. Prospective trial of adipose-derived regenerative cell (ADRC)-enriched fat grafting for partial mastectomy defects: the RESTORE-2 trial. Eur J Surg Oncol. 2012;38(5):382-9.

    Not in our library10.1016/j.ejso.2012.02.178

  113. 113.

    Dos-Anjos Vilaboa S, Navarro-Palou M, Llull R. Age influence on stromal vascular fraction cell yield obtained from human lipoaspirates. Cytotherapy. 2014;16(8):1092-7.

    Not in our library10.1016/j.jcyt.2014.02.007

  114. 114.

    Pak J, Lee JH, Lee SH. Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells. BioMed Res Int. 2014;2014:436029.

    Not in our library10.1155/2014/436029

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    Khan ZA, Dulgar-Tulloch AJ, Rakuff S, Shoemaker PA, Kvam EL, Chen X, et al. Automated systems and methods for isolating regenerative cells from adipose tissue. 2012.

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    Kaengkan P, Baek SE, Kim JY, Kam KY, Do BR, Lee ES, et al. Administration of mesenchymal stem cells and ziprasidone enhanced amelioration of ischemic brain damage in rats. Mol Cells. 2013;36(6):534-41.

    Not in our library10.1007/s10059-013-0235-2

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    Stubbers R, Coleman ME. Apparatus and methods for cell isolation. 2015.

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    Doi K, Tanaka S, Iida H, Eto H, Kato H, Aoi N, et al. Stromal vascular fraction isolated from lipo-aspirates using an automated processing system: bench and bed analysis. J Tissue Eng Regen Med. 2013;7(11):864-70.

    Not in our library10.1002/term.1478

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    Domenis R, Lazzaro L, Calabrese S, Mangoni D, Gallelli A, Bourkoula E, et al. Adipose tissue derived stem cells: in vitro and in vivo analysis of a standard and three commercially available cell-assisted lipotransfer techniques. Stem Cell Res Ther. 2015;6(1):2.

    Not in our library10.1186/scrt536

  121. 121.

    Schafer ME, Hicok KC, Mills DC, Cohen SR, Chao JJ. Acute adipocyte viability after third-generation ultrasound-assisted liposuction. Aesthet Surg J Am Soc Aesthet Plast Surg. 2013;33(5):698-704.

    Not in our library10.1177/1090820x13485239

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    Zhu M, Cohen SR, Hicok KC, Shanahan RK, Strem BM, Yu JC, et al. Comparison of three different fat graft preparation methods: gravity separation, centrifugation, and simultaneous washing with filtration in a closed system. Plast Reconstr Surg. 2013;131(4):873-80.

    Not in our library10.1097/prs.0b013e31828276e9

  123. 123.

    Ansorge H, Garza JR, McCormack MC, Leamy P, Roesch S, Barere A, et al. Autologous fat processing via the Revolve system: quality and quantity of fat retention evaluated in an animal model. Aesthet Surg J Am Soc Aesthet Plast Sur. 2014;34(3):438-47.

    Not in our library10.1177/1090820x14524416

  124. 124.

    Dos-Anjos Vilaboa S, Llull R, Mendel TA. Returning fat grafts to physiologic conditions using washing. Plast Reconstr Surg. 2013;132(2):323e-6.

    Not in our library10.1097/prs.0b013e3182958be1

  125. 125.

    Zimmerlin L, Rubin JP, Pfeifer ME, Moore LR, Donnenberg VS, Donnenberg AD. Human adipose stromal vascular cell delivery in a fibrin spray. Cytotherapy. 2013;15(1):102-8.

    Not in our library10.1016/j.jcyt.2012.10.009

  126. 126.

    Ferguson RE, Cui X, Fink BF, Vasconez HC, Pu LL. The viability of autologous fat grafts harvested with the LipiVage system: a comparative study. Ann Plast Surg. 2008;60(5):594-7.

    Not in our library10.1097/sap.0b013e31817433c5

  127. 127.

    Bianchi F, Maioli M, Leonardi E, Olivi E, Pasquinelli G, Valente S, et al. A new nonenzymatic method and device to obtain a fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Cell Transplant. 2013;22(11):2063-77.

    Not in our library10.3727/096368912x657855

  128. 128.

    García-Contreras M, Messaggio F, Jimenez O, Mendez A. Differences in exosome content of human adipose tissue processed by non-enzymatic and enzymatic methods. CellR4. 2015;3(1):e1423.

    Not in our library

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    Bianchi F, Olivi E, Baldassarre M, Giannone FA, Laggetta M, Valente S, et al. Lipogems, a new modality of fat tissue handling to enhance tissue repair in chronic hind limb ischemia. CellR4. 2014;2(6):e1289.

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    Maioli M, Rinaldi S, Santaniello S, Castagna A, Pigliaru G, Delitala A, et al. Radioelectric asymmetric conveyed fields and human adipose-derived stem cells obtained with a nonenzymatic method and device: a novel approach to multipotency. Cell Transplant. 2014;23(12):1489-500.

    Not in our library10.3727/096368913x672037

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    Carelli S, Messaggio F, Canazza A, Hebda DM, Caremoli F, Latorre E, et al. Characteristics and properties of mesenchymal stem cells derived from micro-fragmented adipose tissue. Cell Transplant. 2014.

    Not in our library10.3727/096368914x681603

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    Raffaini M, Tremolada C. Micro fractured and purified adipose tissue graft (Lipogems®) can improve the orthognathic surgery outcomes both aesthetically and in postoperative healing. CellR4. 2014;2(0):e1118.

    Not in our library

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    Benzi R, Marfia G, Bosetti M, Beltrami G, Magri AS, Versari S et al. Microfractured lipoaspirate may help oral bone and soft tissue regeneration: a case report. CellR4. 2015;3(3):e1583.

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  134. 134.

    Giori A, Tremolada C, Vailati R, Navone SE, Marfia G, Caplan AI. Recovery of function in anal incontinence after micro-fragmented fat graft (Lipogems®) injection: two years follow up of the first 5 cases. CellR4. 2015;3(2):e1544.

    Not in our library

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    Hu CB, Myers KE, Peterson RC. Devices for harvesting and homogenizing adipose tissue containing autologous endothelial cells. 2000.

    Not in our library

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    Victor S. Isolation of stromal vascular fraction from adipose tissue obtained from postmortem source using ultrasonic cavitation. 2014.

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    Bright R, Bright P, Hansen B, Thomas W. Isolation of stem cells from adipose tissue by ultrasonic cavitation, and methods of use. 2014.

    Not in our library

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    Bright R, Bright M, Bright P, Hayne S, Thomas WD. Migraine and tension-type headache treated with stromal vascular fraction: a case series. J Med Case Rep. 2014;8:237.

    Not in our library10.1186/1752-1947-8-237

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    Schafer ME. Selective lysing of cells using ultrasound. 2013.

    Not in our library

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    Gimble JM, Shah FS, Wu X. Non-enzymatic method for isolating human adipose-derived stromal stem cells. 2014.

    Not in our library10.1016/j.jcyt.2013.04.001

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    Michalek J. Method for isolation of adipose tissue-derived stromal vascular fraction cells. 2014.

    Not in our library

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    Hicok KC, Hedrick MH. Automated isolation and processing of adipose-derived stem and regenerative cells. Methods Mol Biol (Clifton, NJ). 2011;702:87-105.

    Not in our library10.1007/978-1-61737-960-4_8

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    Peterson A, Fornace L. Systems, methods and compositions for optimizing tissue and cell enriched grafts. 2010.

    Not in our library

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    Hedrick MH, Fraser JK, Schulzki MJ, Byrnes B, Carlson G, Schreiber RE, et al. Systems and methods for isolating and using clinically safe adipose derived regenerative cells. 2012.

    Not in our library

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    Kakudo N, Morimoto N, Ogawa T, Kusumoto K. Potential of adipose-derived stem cells for regeneration medicine: clinical application and usefulness of fat grafting. J Stem Cell Res Ther. 2014;4(204):2.

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    Sanchez PL, Sanz-Ruiz R, Fernandez-Santos ME, Fernandez-Aviles F. Cultured and freshly isolated adipose tissue-derived cells: fat years for cardiac stem cell therapy. Eur Heart J. 2010;31(4):394-7.

    Not in our library10.1093/eurheartj/ehp403

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    Cimino WW, Llull R, Katz AJ. Tissue processing apparatus and method for processing adipose tissue. 2015.

    Not in our library

  148. 148.

    Llull R, Katz AJ, Cimino WW. Method for processing adipose tissue and processing apparatus. 2013.

    Not in our library

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    Do BR, Lee JK, Kim JH, Pak SH, Shin BS. Peristaltic pump, and regenerative cell extraction system using same. 2013.

    Not in our library

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    Raj SS, Gopal V, Priya N, Krishnegowda B, Thiruvampattil P, Majumdar AS, et al. System for isolating stromal vascular fraction (svf) cells from the adipose tissue and a method thereof. 2015.

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    Williams SK, Kosnik P, England C, Cannon TF, Vossman E, Boland E, et al. Apparatus and methods for preparing tissue grafts. 2007.

    Not in our library

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    Wolters R, Yang A, NELSON J, Williams SK, et al. Hand-held micro-liposuction adipose harvester, processor, and cell concentrator. 2014.

    Not in our library

  153. 153.

    Ariff GD, Cannon T, Case JL, Haller CL, Kosnik P, Luddy CP, et al. Cell separation apparatus and methods of use. 2008.

    Not in our library

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    SHIGEKI S, KIAT OW. Method for isolating stromal vascular fraction. 2015.

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    Buss B. Autologous tissue harvesting and irrigation device. 2012.

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    Kensy A, Winkler KW. Procedure and device for separating adult stem cells from fatty tissue. 2014.

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    Winkler KW, Matthiesen ID. Device for separating adult stem cells. 2013.

    Not in our library

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    Matthiesen I, Winkler KW. Vorrichtung zum Separieren von adulten Stammzellen. 2013.

    Not in our library

  159. 159.

    Victor S. Ultrasonic cavitation derived stromal or mesenchymal vascular extracts and cells derived therefrom obtained from adipose tissue and use thereof. 2013.

    Not in our library

  160. 160.

    Victor S. Isolation of stromal vascular fraction from vascular tissues. 2014.

    Not in our library

  161. 161.

    Cimino WW, Katz AJ, Llull R. Apparatus and methods relating to collecting and processing human biological material containing adipose. 2012.

    Not in our library

  162. 162.

    Vossman E, Iwami S, Yang A, Cannon T, Paek HJ. Adipose tissue collection and pre-processing devices for use in liposuction procedure. 2014.

    Not in our library

  163. 163.

    Tremolada C. Device and method for preparing tissue, particularly adipose tissue. 2013.

    Not in our library

  164. 164.

    Chapman JR, Sparks R. Apparatus for centrifugation and methods therefore. 2013.

    Not in our library

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    Shah FS, Wu X, Dietrich M, Rood J, Gimble JM. A non-enzymatic method for isolating human adipose tissue-derived stromal stem cells. Cytotherapy. 2013;15(8):979-85.

    Not in our library10.1016/j.jcyt.2013.04.001

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