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Clinical application of stem cell therapy in Parkinson's disease

Marios Politis, Olle Lindvall

BMC Medicine · 2012 · Review

doi:10.1186/1741-7015-10-1

Abstract

Cell replacement therapies in Parkinson's disease (PD) aim to provide long-lasting relief of patients' symptoms. Previous clinical trials using transplantation of human fetal ventral mesencephalic (hfVM) tissue in the striata of PD patients have provided proof-of-principle that such grafts can restore striatal dopaminergic (DA-ergic) function. The transplants survive, reinnervate the striatum, and generate adequate symptomatic relief in some patients for more than a decade following operation. However, the initial clinical trials lacked homogeneity of outcomes and were hindered by the development of troublesome graft-induced dyskinesias in a subgroup of patients. Although recent knowledge has provided insights for overcoming these obstacles, it is unlikely that transplantation of hfVM tissue will become routine treatment for PD owing to problems with tissue availability and standardization of the grafts. The main focus now is on producing DA-ergic neuroblasts for transplantation from stem cells (SCs). There is a range of emerging sources of SCs for generating a DA-ergic fate in vitro. However, the translation of these efforts in vivo currently lacks efficacy and sustainability. A successful, clinically competitive SC therapy in PD needs to produce long-lasting symptomatic relief without side effects while counteracting PD progression.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 25, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

Parkinson's disease (PD) is a common neurodegenenerative disorder characterized by the classical motor symptoms of bradykinesia, rigidity and tremor. The pathological hallmark of PD is a gradual loss of nigostriatal dopamine (DA) neurons, but neuronal degeneration also occurs in non-DA-ergic systems. Treatments aiming to relieve PD motor symptoms include the use of oral preparations of L-3,4-dihydroxyphenylalanine (L-DOPA) and DA receptor agonists and, in more advanced cases, the use of apomorphine, delivery of L-DOPA through continuous intestinal administration, and deep brain stimulation in subthalamic nucleus and globus pallidus via surgically implanted electrodes. These treatments have proved effective to a point, but they can generate adverse effects, such as L-DOPA-induced dyskinesias, and they do not counteract the progression of the disease.

Series of studies in PD patients with intrastriatal grafts of human fetal ventral mesencephalic (hfVM) tissue have provided proof-of-principle that cell therapy can work in PD patients, that is, that the dead DA neurons can be replaced by new neurons by transplantation. The grafts can provide DA-ergic reinnervation of the striatum and symptomatic relief lasting as long as 16 years following transplantation in some patients (Figure 1). The most successful operated cases were able to withdraw from L-DOPA therapy. Although some results were promising, the outcomes across the different clinical trials using hfVM tissue have been inconsistent. In addition, the further development of this approach was hindered by the occurrence of adverse effects, so-called graft-induced dyskinesias (GIDs), in a subgroup of patients. Even if new, optimized protocols would improve the safety and efficacy in future hfVM tissue trials, it is doubtful whether transplantation of hfVM tissue will become a mainstream treatment for PD due to shortcomings with tissue availability and standardization of the grafts. In this respect, stem cells (SCs) could provide an unlimited source of well-characterized DA neurons for transplantation and therefore overcome these issues (Figure 2). Here, we aim to discuss what we learned from clinical research with hfVM tissue and also review the current status of SC therapy in PD.

Lessons learned from hfVM tissue clinical trials

Short- and long-term follow-up studies on PD patients subjected to hfVM tissue transplantation have indicated ways of improving the safety and efficacy in future human cell therapy trials. The correct selection of PD patients entering these trials will be of major importance. Positron emission tomography (PET) studies have indicated that the PD patients with the best functional outcome after intrastriatal transplantation of hfVM tissue were the ones in whom the DA-ergic denervation preoperatively was restricted to the dorsal parts of the striatum. Based on these findings, PD patients with more widespread preoperative DA-ergic denervation, including the ventral striatum, should probably be excluded from these trials, as the predictive outcome would be modest or no clinical benefit.

An important breakthrough was the unveiling of one important mechanism underlying GIDs. Studies utilizing PET and clinical observations in previously transplanted PD patients provided strong evidence that GIDs were caused by a graft-derived striatal serotonergic hyperinnervation, possibly engaging in false DA release, which was also weighted by an unfavorable serotonin/DA transporter ratio. Interestingly, the occurrence of GIDs shows a slow and gradual increase compared to the rapid improvement of motor symptoms following transplantation. This difference is likely due to interactions of serotonin and DA neuronal transmissions because of the gradual expansion of graft-derived serotonergic innervation that takes a leading role in regulating synaptic DA levels in the reinnervated areas.

These findings suggested strategies for avoiding the development of GIDs following DA cell therapy with hfVM tissue or SCs in PD. HfVM tissue contains both dopaminergic and serotonergic neuroblasts and the dissection of hfVM tissue should, therefore, be performed in a way to minimize the serotonergic component. Also, when producing DA neurons from SCs, serotonergic neurons should be kept to a minimum or removed by cell sorting. Moreover, culture and storage of the tissue prior to transplantation could change its composition in favor of non-DA-ergic cells. In accordance, previous studies have reported an increased prevalence of GIDs in patients who received tissue that had been stored for long periods compared to those who received fresh tissue. Alternatively, GIDs could be effectively suppressed with systemic administration of serotonin 1A agonists, which dampen transmitter release from serotonergic neurons.

Stem cell therapy in Parkinson's disease

It remains to be shown whether SC-derived DA neurons can efficiently reinnervate the striatum and provide functional recovery in PD patients. Knowledge from hfVM tissue transplantation in animals and humans has provided a number of requirements for establishing a clinically competitive SC-based therapy in PD. The SC grafts should (a) exhibit a regulated release of DA and molecular, electrophysiological, and morphological properties similar to those of substantia nigra neurons; (b) enable survival of more than 100,000 DA neurons per human putamen; (c) reestablish the DA network within the striatum and restore the functional connectivity with host extra-striatal neural circuitries; (d) reverse the motor deficits resembling human symptoms in animal models of PD and induce long-lasting and major symptomatic relief in PD patients; and (e) produce no adverse-effects such as tumor formation, immune reactions and GIDs.

To date, only a few steps have been established towards these goals in vivo. The in vitro generation of SC-derived cells having DA-ergic properties from fetal brain and embryonic SCs (ESCs) and from bone marrow SCs has already been shown (Figure 2). However, it is unclear whether these cells having DA-ergic properties can be used in PD patients. Table 1 summarizes the advantages and disadvantages of different stem cell types for use in PD.

ESCs are highly proliferative and retain pluripotency after extended periods of in vitro expansion. Since they can give rise to any type of cell in the body including DA-ergic neurons, their potential to be useful in a clinical setting seems to be great. Rodent and human ESC-derived DA-ergic neurons have been shown to survive transplantation into the striatum of PD rats and generate some degree of functional recovery. However, studies have shown that the survival of ESC-derived DA-ergic neurons post-transplantation is relatively low. A major concern with using ESC-derived DA-ergic neurons for transplantation in PD patients is the risk of adverse effects such as tumor formation which has been reported in rats. Cell sorting or prolonged differentiation and thereby exhaustion of non-differentiated cell pools in vitro prior to transplantation could potentially reduce the risk of tumor formation.

Another promising source of SCs is adult fibroblasts that are reprogrammed to so-called induced pluripotent SCs (iPSCs) and then differentiated to DA-ergic neurons (Figure 2). The iPSC technology has raised the possibility of generating an unlimited source of PD patient-specific DA-ergic neurons, which theoretically also could be used for autologous transplantation. DA-ergic neurons were first generated from mouse iPSCs, transplanted into the striatum of a rat PD model and shown to ameliorate functional deficits. Recently, DA-ergic neurons were also produced from iPSCs derived from fibroblasts in adult humans and PD patients. Such neurons survived transplantation into the striatum of PD rodents and produced some degree of functional recovery. Potential advantages with the use of iPSCs are that PD patient-specific DA neuroblasts could minimize the immune reactions and eliminate the ethical issues associated with the use of human ESCs. However, as with ESCs, the risk for tumor formation needs to be minimized before iPSC-derived DA-ergic neurons can be considered as an option for transplantation in a clinical setting in PD. Moreover, there are concerns about whether the DA-ergic neurons delivered by autologous transplantation in PD would be more susceptible to the disease pathology because genetic mutations could also be present in the fibroblast-derived cells.

Functional DA-ergic neurons with a substantia nigra phenotype can now also be generated by directly reprogramming mouse and human fibroblasts by expressing neural lineage-specific transcription factors (Figure 2). This conversion does not occur through a pluripotent SC stage and thereby the risk of tumor formation is eliminated. Before their clinical use in PD is considered, it is necessary to show that the directly converted DA-ergic neurons can survive transplantation and give rise to substantial improvements in animal models.

Fetal brain neural SC (NSC)-derived DA-ergic neurons (Figure 2) are associated with lower risk of tumor formation and immune rejection than ESCs. Early studies reported that non-differentiated NSCs taken from a human source and transplanted in rats have limited differentiation in vivo and only partially affect PD-like symptoms. A more recent study showed that non-differentiated NSCs implanted into PD primates survived, migrated, and had a functional impact. A small number of NSC progeny differentiated into DA phenotypes. The use of developmental signals such as sonic hedgehog, Wnt5a and others in fetal NSC differentiation in vitro enhances the DA-ergic yield and multiple signals can have synergistic effects. Production of fetal NSC-derived DA-ergic neurons through well-controlled differentiation protocols in vitro should ensure better homogeneity between grafts.

Bone marrow-derived stromal cells and mesenchymal SCs (MSCs) have been proposed as potential cell sources for transplantation in PD (Figure 2). It has been reported that non-differentiated murine MSCs are able to differentiate into tyrosine hydroxylase-positive neurons and improve motor performance in mice. Also, it has been demonstrated that cells with DA-ergic properties can be produced from both rat and human MSCs, and that transplantation of these cells gave rise to improvement of motor function in an animal model of PD. More recently, a clinical trial in advanced PD patients using unilateral transplantation of autologous bone marrow-derived MSCs into the sublateral ventricular zone reported modest clinical improvement with no adverse effects such as tumor formation at 12 months. In this trial, there were no PET assessments before and after transplantation in order to determine graft survival or changes of DA-ergic striatal function. Thus, the mechanisms underlying the reported modest improvements are completely unknown. Further preclinical work is needed for investigating the ability of MSCs to differentiate into DA-ergic neurons and to reverse functional deficits in animal models.

Conclusions

Although the ability to restore function in PD patients by DA-ergic neuron replacement has been demonstrated to some extent with hfVM tissue, the focus is now on producing standardized DA-ergic neuroblasts from SCs for transplantation. ESCs and iPSCs seem the simplest to manipulate towards a DA-ergic fate and to produce large numbers of DA-ergic neurons in vitro, but fetal brain NSCs could also be useful for clinical application. Both iPSC-derived and directly converted DA-ergic neurons have one more advantage as they potentially can be used for autologous transplantation in PD patients.

Several important in vivo properties, which will be decisive for the success or failure of a clinical trial in PD, remain to be demonstrated for human SC-derived DA-ergic neurons in animal models. These include the ability of the SC-derived DA-ergic neurons to substantially reinnervate striatum, restore DA release and markedly improve PD symptoms. Before going ahead with human trials using transplantation of SC-derived DA-ergic neurons, the risks for tumor formation, immune reactions, and development of GIDs need to be tested and proven minimal. Major research efforts will be needed for the development of a clinically competitive SC-based therapy, which for the first time opens up the possibility for an effective restorative treatment for PD patients.

List of abbreviations

DA: dopamine; DA-ergic: dopaminergic; ESCs: embryonic stem cells; GIDs: graft-induced dyskinesias; hfVM: human fetal ventral mesencephalic; iPSCs: induced pluripotent stem cells; L-DOPA: L-3,4-dihydroxyphenylalanine; MSCs: mesenchymal stem cells; NSCs: neural stem cells; PD: Parkinson's disease; PET: positron emission tomography; SCs: stem cells.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

MP and OL are equally responsible for the content of this article. Both authors read and approved the final manuscript.

Pre-publication history

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/1741-7015/10/1/prepub

References 57

  1. 1.

    Politis M Wu K Loane C Kiferle L Molloy S Brooks DJ Piccini P Staging of serotonergic dysfunction in Parkinson's disease: an in vivo 11C-DASB PET studyNeurobiol Dis2010 40216221

    Not in our library10.1016/j.nbd.2010.05.028

  2. 2.

    Dunnett SB Björklund A Lindvall O Cell therapy in Parkinson's disease - stop or go?Nat Rev Neurosci2001 2365369

    Not in our library10.1038/35072572

  3. 3.

    Lindvall O Björklund A Cell therapy in Parkinson's diseaseNeuroRx2004 1382393

    Not in our library10.1602/neurorx.1.4.382

  4. 4.

    Politis M Wu K Loane C Quinn NP Brooks DJ Rehncrona S Bjorklund A Lindvall O Piccini P Serotonergic neurons mediate dyskinesia side effects in Parkinson's patients with neural transplantsSci Transl Med2010 238ra46

    Not in our library10.1126/scitranslmed.3000976

  5. 5.

    Politis M Oertel WH Wu K Quinn NP Pogarell O Brooks DJ Bjorklund A Lindvall O Piccini P Graft-induced dyskinesias in Parkinson's disease: High striatal serotonin/dopamine transporter ratioMov Disord2011 1119972003

    Not in our library10.1002/mds.23743

  6. 6.

    Freed CR Greene PE Breeze RE Tsai WY DuMouchel W Kao R Dillon S Winfield H Culver S Trojanowski JQ Eidelberg D Fahn S Transplantation of embryonic dopamine neurons for severe Parkinson's diseaseN Engl J Med2001 344710719

    Not in our library10.1056/nejm200103083441002

  7. 7.

    Hagell P Piccini P Björklund A Brundin P Rehncrona S Widner H Crabb L Pavese N Oertel WH Quinn N Brooks DJ Lindvall O Dyskinesias following neural transplantation in Parkinson's diseaseNat Neurosci2002 5627628

    Not in our library10.1038/nn863

  8. 8.

    Olanow CW Goetz CG Kordower JH Stoessl AJ Sossi V Brin MF Shannon KM Nauert GM Perl DP Godbold J Freeman TB A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's diseaseAnn Neurol2003 54403414

    Not in our library10.1002/ana.10720

  9. 9.

    Piccini P Pavese N Hagell P Reimer J Björklund A Oertel WH Quinn NP Brooks DJ Lindvall O Factors affecting the clinical outcome after neural transplantation in Parkinson's diseaseBrain2005 12829772986

    Not in our library10.1093/brain/awh649

  10. 10.

    Ma Y Tang C Chaly T Greene P Breeze R Fahn S Freed C Dhawan V Eidelberg D Dopamine cell implantation in Parkinson's disease: long-term clinical and (18)F-FDOPA PET outcomesJ Nucl Med2010 51715

    Not in our library10.2967/jnumed.109.066811

  11. 11.

    Politis M Dyskinesias after neural transplantation in Parkinson's disease: what do we know and what is next?BMC Med2010 880

    Not in our library10.1186/1741-7015-8-80

  12. 12.

    Daszuta A Strecker RE Brundin P Björklund A Serotonin neurons grafted to the adult rat hippocampus. I. Time course of growth as studied by immunohistochemistry and biochemistryBrain Res1988 458119

    Not in our library10.1016/0006-8993(88)90490-8

  13. 13.

    Carlsson T Carta M Winkler C Björklund A Kirik D Serotonin neuron transplants exacerbate L-DOPA-induced dyskinesias in a rat model of Parkinson's diseaseJ Neurosci2007 2780118022

    Not in our library10.1523/jneurosci.2079-07.2007

  14. 14.

    Braak H Del Tredici K Assessing fetal nerve cell grafts in Parkinson's diseaseNat Med2008 14483485

    Not in our library10.1038/nm0508-483

  15. 15.

    Fawcett JW Barker RA Dunnett SB Dopaminergic neuronal survival and the effects of bFGF in explant, three dimensional and monolayer cultures of embryonic rat ventral mesencephalonExp Brain Res1995 106275282

    Not in our library10.1007/bf00241123

  16. 16.

    Isacson O Bjorklund LM Schumacher JM Toward full restoration of synaptic and terminal function of the dopaminergic system in Parkinson's disease by stem cellsAnn Neurol2003 53Suppl 3135148

    Not in our library10.1002/ana.10482

  17. 17.

    Mendez I Sanchez-Pernaute R Cooper O Viñuela A Ferrari D Björklund L Dagher A Isacson O Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's diseaseBrain2005 12814981510

    Not in our library10.1093/brain/awh510

  18. 18.

    Hagell P Brundin P Cell survival and clinical outcome following intrastriatal transplantation in Parkinson diseaseJ Neuropathol Exp Neurol2001 60741752

    Not in our library10.1093/jnen/60.8.741

  19. 19.

    Piccini P Lindvall O Björklund A Brundin P Hagell P Ceravolo R Oertel W Quinn N Samuel M Rehncrona S Widner H Brooks DJ Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic graftsAnn Neurol2000 48689695

    Not in our library10.1002/1531-8249(200011)48:5<689::aid-ana1>3.0.co;2-n

  20. 20.

    Dezawa M Kanno H Hoshino M Cho H Matsumoto N Itokazu Y Tajima N Yamada H Sawada H Ishikawa H Mimura T Kitada M Suzuki Y Ide C Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantationJ Clin Invest2004 11317011710

    Not in our library10.1172/jci20935

  21. 21.

    Lindvall O Kokaia Z Martinez-Serrano A Stem cell therapy for human neurodegenerative disorders-how to make it workNat Med2004 10SupplS4250

    Not in our library10.1038/nm1064

  22. 22.

    Takagi Y Takahashi J Saiki H Morizane A Hayashi T Kishi Y Fukuda H Okamoto Y Koyanagi M Ideguchi M Hayashi H Imazato T Kawasaki H Suemori H Omachi S Iida H Itoh N Nakatsuji N Sasai Y Hashimoto N Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate modelJ Clin Invest2005 115102109

    Not in our library10.1172/jci21137

  23. 23.

    Amit M Carpenter MK Inokuma MS Chiu CP Harris CP Waknitz MA Itskovitz-Eldor J Thomson JA Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of cultureDev Biol2000 227271278

    Not in our library10.1006/dbio.2000.9912

  24. 24.

    Park S Lee KS Lee YJ Shin HA Cho HY Wang KC Kim YS Lee HT Chung KS Kim EY Lim J Generation of dopaminergic neurons in vitro from human embryonic stem cells treated with neurotrophic factorsNeurosci Lett2004 35999103

    Not in our library10.1016/j.neulet.2004.01.073

  25. 25.

    Perrier AL Tabar V Barberi T Rubio ME Bruses J Topf N Harrison NL Studer L Derivation of midbrain dopamine neurons from human embryonic stem cellsProc Natl Acad Sci USA2004 1011254312548

    Not in our library10.1073/pnas.0404700101

  26. 26.

    Cho MS Lee YE Kim JY Chung S Cho YH Kim DS Kang SM Lee H Kim MH Kim JH Leem JW Oh SK Choi YM Hwang DY Chang JW Kim DW Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cellsProc Natl Acad Sci USA2008 10533923397

    Not in our library10.1073/pnas.0712359105

  27. 27.

    Kim JH Auerbach JM Rodríguez-Gómez JA Velasco I Gavin D Lumelsky N Lee SH Nguyen J Sánchez-Pernaute R Bankiewicz K McKay R Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's diseaseNature2002 4185056

    Not in our library10.1038/nature00900

  28. 28.

    Ben-Hur T Idelson M Khaner H Pera M Reinhartz E Itzik A Reubinoff BE Transplantation of human embryonic stem cell-derived neural progenitors improves behavioral deficit in Parkinsonian ratsStem Cells2004 2212461255

    Not in our library10.1634/stemcells.2004-0094

  29. 29.

    Roy NS Cleren C Singh SK Yang L Beal MF Goldman SA Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytesNat Med2006 1212591268

    Not in our library10.1038/nm1495

  30. 30.

    Yang D Zhang ZJ Oldenburg M Ayala M Zhang SC Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian ratsStem Cells2008 265563

    Not in our library10.1634/stemcells.2007-0494

  31. 31.

    Brederlau A Correia AS Anisimov SV Elmi M Paul G Roybon L Morizane A Bergquist F Riebe I Nannmark U Carta M Hanse E Takahashi J Sasai Y Funa K Brundin P Eriksson PS Li JY Transplantation of human embryonic stem cell-derived cells to a rat model of Parkinson's disease: effect of in vitro differentiation on graft survival and teratoma formationStem Cells2006 2414331440

    Not in our library10.1634/stemcells.2005-0393

  32. 32.

    Hedlund E Pruszak J Lardaro T Ludwig W Viñuela A Kim KS Isacson O Embryonic stem cell-derived Pitx3-enhanced green fluorescent protein midbrain dopamine neurons survive enrichment by fluorescence-activated cell sorting and function in an animal model of Parkinson's diseaseStem Cells2008 2615261536

    Not in our library10.1634/stemcells.2007-0996

  33. 33.

    Takahashi K Yamanaka S Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factorsCell2006 126663676

    Not in our library10.1016/j.cell.2006.07.024

  34. 34.

    Park IH Arora N Huo H Maherali N Ahfeldt T Shimamura A Lensch MW Cowan C Hochedlinger K Daley GQ Disease-specific induced pluripotent stem cellsCell2008 134877886

    Not in our library10.1016/j.cell.2008.07.041

  35. 35.

    Tabar V Tomishima M Panagiotakos G Wakayama S Menon J Chan B Mizutani E Al-Shamy G Ohta H Wakayama T Studer L Therapeutic cloning in individual parkinsonian miceNat Med2008 14379381

    Not in our library10.1038/nm1732

  36. 36.

    Wernig M Zhao JP Pruszak J Hedlund E Fu D Soldner F Broccoli V Constantine-Paton M Isacson O Jaenisch R Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's diseaseProc Natl Acad Sci USA2008 10558565861

    Not in our library10.1073/pnas.0801677105

  37. 37.

    Soldner F Hockemeyer D Beard C Gao Q Bell GW Cook EG Hargus G Blak A Cooper O Mitalipova M Isacson O Jaenisch R Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factorsCell2009 136964977

    Not in our library10.1016/j.cell.2009.02.013

  38. 38.

    Cai J Yang M Poremsky E Kidd S Schneider JS Iacovitti L Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned ratsStem Cells Dev2010 1910171023

    Not in our library10.1089/scd.2009.0319

  39. 39.
    Efficient Generation of Functional Dopaminergic Neurons from Human Induced Pluripotent Stem Cells Under Defined Conditions · 2010
    No notice
  40. 40.

    Hargus G Cooper O Deleidi M Levy A Lee K Marlow E Yow A Soldner F Hockemeyer D Hallett PJ Osborn T Jaenisch R Isacson O Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian ratsProc Natl Acad Sci USA2010 1071592115926

    Not in our library10.1073/pnas.1010209107

  41. 41.

    Li JY Englund E Holton JL Soulet D Hagell P Lees AJ Lashley T Quinn NP Rehncrona S Björklund A Widner H Revesz T Lindvall O Brundin P Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagationNat Med2008 14501503

    Not in our library10.1038/nm1746

  42. 42.

    Kordower JH Chu Y Hauser RA Freeman TB Olanow CW Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's diseaseNat Med2008 14504506

    Not in our library10.1038/nm1747

  43. 43.

    Vierbuchen T Ostermeier A Pang ZP Kokubu Y Südhof TC Wernig M Direct conversion of fibroblasts to functional neurons by defined factorsNature2010 46310351041

    Not in our library10.1038/nature08797

  44. 44.

    Pfisterer U Kirkeby A Torper O Wood J Nelander J Dufour A Björklund A Lindvall O Jakobsson J Parmar M Direct conversion of human fibroblasts to dopaminergic neuronsProc Natl Acad Sci USA2011 1081034310348

    Not in our library10.1073/pnas.1105135108

  45. 45.

    Caiazzo M Dell'anno MT Dvoretskova E Lazarevic D Taverna S Leo D Sotnikova TD Menegon A Roncaglia P Colciago G Russo G Carninci P Pezzoli G Gainetdinov RR Gustincich S Dityatev A Broccoli V Direct generation of functional dopaminergic neurons from mouse and human fibroblastsNature2011 476224227

    Not in our library10.1038/nature10284

  46. 46.

    Mimeault M Batra SK Concise review: recent advances on the significance of stem cells in tissue regeneration and cancer therapiesStem Cells2006 2423192345

    Not in our library10.1634/stemcells.2006-0066

  47. 47.

    Svendsen CN Caldwell MA Shen J ter Borg MG Rosser AE Tyers P Karmiol S Dunnett SB Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's diseaseExp Neurol1997 148135146

    Not in our library10.1006/exnr.1997.6634

  48. 48.

    Redmond DE Jr Bjugstad KB Teng YD Ourednik V Ourednik J Wakeman DR Parsons XH Gonzalez R Blanchard BC Kim SU Gu Z Lipton SA Markakis EA Roth RH Elsworth JD Sladek JR Jr Sidman RL Snyder EY Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cellsProc Natl Acad Sci USA2007 1041217512180

    Not in our library10.1073/pnas.0704091104

  49. 49.

    Wang MZ Jin P Bumcrot DA Marigo V McMahon AP Wang EA Woolf T Pang K Induction of dopaminergic neuron phenotype in the midbrain by Sonic hedgehog proteinNat Med1995 111841188

    Not in our library10.1038/nm1195-1184

  50. 50.

    Ye W Shimamura K Rubenstein JL Hynes MA Rosenthal A FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plateCell1998 93755766

    Not in our library10.1016/s0092-8674(00)81437-3

  51. 51.

    Andersson EK Irvin DK Ahlsiö J Parmar M Ngn2 and Nurr1 act in synergy to induce midbrain dopaminergic neurons from expanded neural stem and progenitor cellsExp Cell Res2007 31311721180

    Not in our library10.1016/j.yexcr.2006.12.014

  52. 52.

    O'Keeffe FE Scott SA Tyers P O'Keeffe GW Dalley JW Zufferey R Caldwell MA Induction of A9 dopaminergic neurons from neural stem cells improves motor function in an animal model of Parkinson's diseaseBrain2008 131630641

    Not in our library10.1093/brain/awm340

  53. 53.

    Parish CL Castelo-Branco G Rawal N Tonnesen J Sorensen AT Salto C Kokaia M Lindvall O Arenas E Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian miceJ Clin Invest2008 118149160

    Not in our library10.1172/jci32273

  54. 54.

    Rössler R Boddeke E Copray S Differentiation of non-mesencephalic neural stem cells towards dopaminergic neuronsNeuroscience2010 170417428

    Not in our library10.1016/j.neuroscience.2010.07.023

  55. 55.

    Li Y Chen J Wang L Zhang L Lu M Chopp M Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's diseaseNeurosci Lett2001 3166770

    Not in our library10.1016/s0304-3940(01)02384-9

  56. 56.

    Venkataramana NK Kumar SK Balaraju S Radhakrishnan RC Bansal A Dixit A Rao DK Das M Jan M Gupta PK Totey SM Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's diseaseTransl Res2010 1556270

    Not in our library10.1016/j.trsl.2009.07.006

  57. 57.

    Politis M Optimizing functional imaging protocols for assessing the outcome of fetal cell transplantation in Parkinson's diseaseBMC Med2011 950

    Not in our library10.1186/1741-7015-9-50

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