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Cells therapy for Parkinson’s disease—so close and so far away

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Abstract

One of the strategies of treating Parkinson’s disease (PD) is the replacement of lost neurons in the substantia nigra with healthy dapamingergic cells. Potential sources for cells range from autologous grafts of dopamine secreting cells, fetal ventral mesencephalon tissue, to various stem cell types. Over the past quarter century, many experimental replacement therapies have been tried on PD animal models as well as human patients, yet none resulted in satisfactory outcomes that warrant wide applications. Recent progress in stem cell biology has shown that nuclear transfer embryonic stem cells (ntES) or induced pluripotent stem cells (iPS) derived cells can be used to successfully treat rodent PD models, thus solving the problem of immunorejection and paving the way for future autologous transplantations for treating PD. Meanwhile, however, post mortem analysis of patients who received fetal brain cell transplantation revealed that implanted cells are prone to degeneration just like endogenous neurons in the same pathological area, indicating long-term efficacy of cell therapy of PD needs to overcome the degenerating environment in the brain. A better understanding of neurodegeneration in the midbrain appeared to be a necessary step in developing new cell therapies in Parkinson’s disease. It is likely that future cell replacement will focus on not only ameliorating symptoms of the disease but also trying to slow the progression of the disease by either neuroprotection or restoring the micro-environment in the midbrain.

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References

  1. Lindvall O, Brundin P, Widner H, et al. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science, 1990, 247: 574–577, 2105529, 10.1126/science.2105529, 1:STN:280:DyaK3c7ktVOhtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  2. Freed C R, Greene P E, Breeze R E, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med, 2001, 344: 710–719, 11236774, 10.1056/NEJM200103083441002, 1:STN:280:DC%2BD3M7ltFCisQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  3. Olanow C W, Goetz C G, Kordower J H, et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol, 2003, 54: 403–414, 12953276, 10.1002/ana.10720

    Article  PubMed  Google Scholar 

  4. Li J Y, Englund E, Holton J L, et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med, 2008, 14: 501–503, 18391963, 10.1038/nm1746, 1:CAS:528:DC%2BD1cXlsFCmsrs%3D

    Article  PubMed  CAS  Google Scholar 

  5. Kordower J H, Chu Y, Hauser R A, et al. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med, 2008, 14: 504–506, 18391962, 10.1038/nm1747, 1:CAS:528:DC%2BD1cXlsFCmsrg%3D

    Article  PubMed  CAS  Google Scholar 

  6. Mendez I, Vinuela A, Astradsson A, et al. Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years. Nat Med, 2008, 14: 507–509, 18391961, 10.1038/nm1752, 1:CAS:528:DC%2BD1cXlsFCmsrc%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Newman M B, Bakay R A. Therapeutic potentials of human embryonic stem cells in Parkinson’s disease. Neurotherapeutics, 2008, 5: 237–251, 18394566, 10.1016/j.nurt.2008.02.004, 1:CAS:528:DC%2BD1cXmtFOltLY%3D

    Article  PubMed  CAS  Google Scholar 

  8. Bjugstad K B, Teng Y D, Redmond D E Jr, et al. Human neural stem cells migrate along the nigrostriatal pathway in a primate model of Parkinson’s disease. Exp Neurol, 2008, 211: 362–369, 18394605, 10.1016/j.expneurol.2008.01.025, 1:CAS:528:DC%2BD1cXmtVWqsLc%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Tabar V, Tomishima M, Panagiotakos G, et al. Therapeutic cloning in individual parkinsonian mice. Nat Med, 2008, 14: 379–381, 18376409, 10.1038/nm1732, 1:CAS:528:DC%2BD1cXktl2is7Y%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Yamanaka S. Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell, 2007, 1: 39–49, 18371333, 10.1016/j.stem.2007.05.012, 1:CAS:528:DC%2BD2sXptV2rsrk%3D

    Article  PubMed  CAS  Google Scholar 

  11. Pardal R, Ortega-Sáenz P, Durán R, et al. Glia-like stem cells sustain physiologic neurogenesis in the adult mammalian carotid body. Cell, 2007, 131: 364–377, 17956736, 10.1016/j.cell.2007.07.043, 1:CAS:528:DC%2BD2sXht1KqsbbF

    Article  PubMed  CAS  Google Scholar 

  12. Park H J, Lee P H, Bang O Y, et al. Mesenchymal stem cells therapy exerts neuroprotection in a progressive animal model of Parkinson’s disease. J Neurochem, 2008, 107: 141–151, 18665911, 10.1111/j.1471-4159.2008.05589.x, 1:CAS:528:DC%2BD1cXht1KgtLbE

    Article  PubMed  CAS  Google Scholar 

  13. Friling S, Andersson E, Thompson L H, et al. Efficient production of mesencephalic dopamine neurons by Lmx1a expression in embryonic stem cells. Proc Natl Acad Sci USA, 2009, 106: 7613–7618, 19383789, 10.1073/pnas.0902396106, 1:CAS:528:DC%2BD1MXmt1Krsr4%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  14. Shimada H, Yoshimura N, Tsuji A, et al. Differentiation of dopaminergic neurons from human embryonic stem cells: modulation of differentiation by FGF-20. J Biosci Bioeng, 2009, 107: 447–454, 19332307, 10.1016/j.jbiosc.2008.12.013, 1:CAS:528:DC%2BD1MXntlegtL8%3D

    Article  PubMed  CAS  Google Scholar 

  15. Lee S H, Lumelsky N, Studer L, et al. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol, 2000, 18: 675–679, 10835609, 10.1038/76536, 1:CAS:528:DC%2BD3cXktlWjs70%3D

    Article  PubMed  CAS  Google Scholar 

  16. Bjorklund L M, Sánchez-Pernaute R, Chung S, et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA, 2002, 99: 2344–2349, 11782534, 10.1073/pnas.022438099, 1:CAS:528:DC%2BD38XitVSrurg%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 2006, 126: 663–676, 16904174, 10.1016/j.cell.2006.07.024, 1:CAS:528:DC%2BD28Xpt1aktbs%3D

    Article  PubMed  CAS  Google Scholar 

  18. Wernig M, Zhao J P, Pruszak J, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc Natl Acad Sci USA, 2008, 105: 5856–5861, 18391196, 10.1073/pnas.0801677105, 1:CAS:528:DC%2BD1cXltVyis70%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Svendsen C. Stem cells and Parkinson’s disease: toward a treatment, not a cure. Cell Stem Cell, 2008, 2: 412–413, 18462691, 10.1016/j.stem.2008.04.010, 1:CAS:528:DC%2BD1cXmt1Wrs78%3D

    Article  PubMed  CAS  Google Scholar 

  20. McKay R, Kittappa R. Will stem cell biology generate new therapies for Parkinson’s disease? Neuron, 2008, 58: 659–661, 18549778, 10.1016/j.neuron.2008.05.016, 1:CAS:528:DC%2BD1cXnvVSqsbs%3D

    Article  PubMed  CAS  Google Scholar 

  21. Espejo E F, Montoro R J, Armengol J A, et al. Cellular and functional recovery of Parkinsonian rats after intrastriatal transplantation of carotid body cell aggregates. Neuron, 1998, 20: 197–206, 9491982, 10.1016/S0896-6273(00)80449-3, 1:CAS:528:DyaK1cXhtlGns7k%3D

    Article  PubMed  CAS  Google Scholar 

  22. Toledo-Aral J J, Méndez-Ferrer S, Pardal R, et al. Dopaminergic cells of the carotid body: Physiological significance and possible therapeutic applications in Parkinson’s disease. Brain Res Bull, 2002, 57: 847–853, 12031283, 10.1016/S0361-9230(01)00771-7, 1:CAS:528:DC%2BD38XjvVGitrw%3D

    Article  PubMed  CAS  Google Scholar 

  23. Kokovay E, Temple S. Taking neural crest stem cells to new heights. Cell, 2007, 131: 234–236, 17956725, 10.1016/j.cell.2007.10.006, 1:CAS:528:DC%2BD2sXht1KqsbnE

    Article  PubMed  CAS  Google Scholar 

  24. Hong M, Mukhida K, Mendez I. GDNF therapy for Parkinson’s disease. Expert Rev Neurother, 2008, 8: 1125–1139, 18590482, 10.1586/14737175.8.7.1125, 1:CAS:528:DC%2BD1cXnvFShs7s%3D

    Article  PubMed  CAS  Google Scholar 

  25. Gill S S, Patel N K, Hotton G R, et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med, 2003, 9: 589–595, 12669033, 10.1038/nm850, 1:CAS:528:DC%2BD3sXjtlamtLw%3D

    Article  PubMed  CAS  Google Scholar 

  26. Patel N K, Bunnage M, Plaha P, et al. Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: a two-year outcome study. Ann Neurol (2005). 57: 298–302, 15668979, 10.1002/ana.20374, 1:CAS:528:DC%2BD2MXhs1Citr8%3D

    Article  PubMed  CAS  Google Scholar 

  27. Slevin J T, Gerhardt G A, Smith C D, et al. Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg, 2005, 102: 216–222, 15739547, 10.3171/jns.2005.102.2.0216, 1:CAS:528:DC%2BD2MXhslygs7s%3D

    Article  PubMed  CAS  Google Scholar 

  28. Peck P. Amgen decision to halt GDNF clinical trials and withdraw the drug triggers protest from researchers and patients. Neurol Today, Am Acad Neurol, 2005, 5: 4, 7, 24

    Article  Google Scholar 

  29. Nutt J G, Burchiel K J, Comella C L, et al. Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology, 2003, 60: 69–73, 12525720, 1:CAS:528:DC%2BD38Xps1aiur8%3D

    Article  PubMed  CAS  Google Scholar 

  30. Morrison P F, Lonser R R, Oldfield E H. Convective delivery of glial cell line-derived neurotrophic factor in the human putamen. J Neurosurg, 2007, 107: 74–83, 17639877, 10.3171/JNS-07/07/0074

    Article  PubMed  Google Scholar 

  31. Elsworth J D, Redmond D E Jr, Leranth C, et al. AAV2-mediated gene transfer of GDNF to the striatum of MPTP monkeys enhances the survival and outgrowth of co-implanted fetal dopamine neurons. Exp Neurol, 2008, 211: 252–258, 18346734, 10.1016/j.expneurol.2008.01.026, 1:CAS:528:DC%2BD1cXlsF2qtLk%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Emborg M E, Ebert A D, Moirano J, et al. GDNF-secreting human neural progenitor cells increase tyrosine hydroxylase and VMAT2 expression in MPTP-treated cynomolgus monkeys. Cell Transplant, 2008, 17: 383–395, 18522241

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Cell Therapy Center, Xuanwu Hospital, Capital Medical University and Key Laboratory of Neurodegeneration, Ministry of Education, Beijing, 100053, China

    ZhenHua Ren & Yu Zhang

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  1. ZhenHua Ren
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  2. Yu Zhang
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Correspondence to Yu Zhang.

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Support by the National Key Basic Research and Development Program of China (Grant No. 2006CB0F0603) and Science and Technology Plan, Beijing Municipal Science & Technology Commission (Grant No. H020220010290)

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Ren, Z., Zhang, Y. Cells therapy for Parkinson’s disease—so close and so far away. SCI CHINA SER C 52, 610–614 (2009). https://doi.org/10.1007/s11427-009-0090-8

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  • DOI: https://doi.org/10.1007/s11427-009-0090-8

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