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Cell Therapy in Parkinson’s Disease

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Stem Cell Biology in Health and Disease

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the substantia nigra. It is typically treated symptomatically by dopamine replacement using either levodopa or dopamine agonists, however, cell therapies that aim to repair and replace these lost neurons and their projections to the striatum represent a very promising strategy to help cure people of this condition. Several cell sources have been considered for this use including fetal ventral mesencephalon, embryonic stem cells and induced pluripotent stem cells. Some of them have gone into the clinical arena with mixed results, whilst others still remain purely experimental. In this chapter we will discuss the stage of development of each of them and the pros and cons of their use for the treatment of PD.

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References

  1. Gill SS, Hotton GR, O’Sullivan K et al. (2003) Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Nat Med 9:589–595.

    Article  PubMed  CAS  Google Scholar 

  2. Patel NK, Plaha P, Svendsen CN et al. (2005) Intraputamenal infusion of glial cell line-derived neurotrophic factor in PD: a two-year outcome study. Ann Neurol 57:298–302.

    Article  PubMed  CAS  Google Scholar 

  3. Lang AE, Patel NK, Lozano A et al. (2006) Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson’s disease. Ann Neurol 59:459–466.

    Article  PubMed  CAS  Google Scholar 

  4. Perlow MJ, Freed WJ, Hoffer BJ et al. (1979) Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science 204:643–647.

    Article  PubMed  CAS  Google Scholar 

  5. Bjorklund A and Stenevi U (1979) Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 177:555–560.

    Article  PubMed  CAS  Google Scholar 

  6. Brundin P, Nilsson OG, Strecker RE et al. (1986) Behavioral effects of human fetal dopamine neurons grafted in a rat model of Parkinson’s disease. Exp Brain Res 65:235–240.

    Article  PubMed  CAS  Google Scholar 

  7. Freed CR, Breeze RE, Rosenberg NL et al. (1992) Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson’s disease. N Engl J Med 327:1549–1555.

    Article  PubMed  CAS  Google Scholar 

  8. Hagell P, Piccini P, Jahanshahi M et al. (1999) Sequential bilateral transplantation in Parkinson’s disease: Effects of the second graft. Brain 122:1121–1132.

    Article  PubMed  Google Scholar 

  9. Hauser RA, Snow BJ, Nauert M et al. (1999) Long-term evaluation of bilateral fetal nigral transplantation in Parkinson’s disease. Arch Neurol 56:179–187.

    Article  PubMed  CAS  Google Scholar 

  10. Brundin P, Hagell P, Piccini P et al. (2000) Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson’s disease. Brain 123:1380–1390.

    Article  PubMed  Google Scholar 

  11. Freed CR, Breeze RE, Tsai WY et al. (2001) Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Eng J Med 344:710–719.

    Article  CAS  Google Scholar 

  12. Olanow CW, Kordower JH, Stoessl AJ et al. (2003) A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 54:403–414.

    Article  PubMed  Google Scholar 

  13. Studer L, McKay RD (1998) Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nat Neurosci 1:290–295.

    Article  PubMed  CAS  Google Scholar 

  14. Storch A, Csete M, Boehm BO et al. (2001) Long-term proliferation and dopaminergic differentiation of human mesencephalic neural precursor cells. Exp Neurol 170:317–325.

    Article  PubMed  CAS  Google Scholar 

  15. Mukhida K, Baghbaderani BA, Hong M et al. (2008) Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats. Neurosurg Focus 24:E8.

    Article  PubMed  Google Scholar 

  16. Jensen P, Pedersen EG, Zimmer J et al. (2008) Functional effect of FGF2- and FGF8-expanded ventral mesencephalic precursor cells in a rat model of Parkinson’s disease. Brain Res 1218:13–20.

    Article  PubMed  CAS  Google Scholar 

  17. Jain M, Armstrong RJ, Tyers P et al. (2003) GABAergic immunoreactivity is predominant in neurons derived from expanded human neural precursor cells in vitro. Exp Neurol 182:113–123.

    Article  PubMed  CAS  Google Scholar 

  18. Sanchez-Pernaute R, Bankiewicz KS, Major EO et al. (2001) In vitro generation and transplantation of precursor-derived human dopamine neurons. J Neurosci Res 65:284–288.

    Article  PubMed  CAS  Google Scholar 

  19. Studer L, Csete M, Lee SH et al. (2000) Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen. J Neurosci 20:7377–7383.

    PubMed  CAS  Google Scholar 

  20. Parish CL, Castelo-Branco G, Rawal N et al. (2008) Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice. J Clin Invest 118:149–160.

    Article  PubMed  CAS  Google Scholar 

  21. Kawasaki H, Mizuseki K, Nishikawa S et al. (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28:31–40.

    Article  PubMed  CAS  Google Scholar 

  22. Lee SH, Studer L, Auerbach JM, et al. (2000) Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotech 18:675–679.

    Article  CAS  Google Scholar 

  23. Kim JH, Rodriguez-Gomez JA, Velasco I et al. (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56.

    Article  PubMed  CAS  Google Scholar 

  24. Kim DW, Chung S, Hwang M et al. (2006). Stromal cell-derived inducing activity, Nurr1, and signaling molecules synergistically induce dopaminergic neurons from mouse embryonic stem cells. Stem Cells 24:557–567.

    Article  PubMed  CAS  Google Scholar 

  25. Perrier AL, Tabar V, Barberi T et al. (2004) Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci USA 101:12543–12548.

    Article  PubMed  CAS  Google Scholar 

  26. Yang D, Zhang ZJ, Oldenburg M et al. (2008) Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats. Stem Cells 26:55–63.

    Article  PubMed  CAS  Google Scholar 

  27. Li JY, Christophersen NS, Hall V et al. (2008) Critical issues of clinical human embryonic stem cell therapy for brain repair. Trends Neurosci 31:146–153.

    Article  PubMed  Google Scholar 

  28. Roy NS, Cleren C, Singh SK et al. (2006) Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat Med 12:1259–1268.

    Article  PubMed  CAS  Google Scholar 

  29. Taylor CJ, Bolton EM, Pocock S et al. (2005) Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet 366:2019–2025.

    Article  PubMed  Google Scholar 

  30. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676.

    Article  PubMed  CAS  Google Scholar 

  31. Takahashi K, Tanabe K, Ohnuki M et al. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872.

    Article  PubMed  CAS  Google Scholar 

  32. Nakagawa M, Koyanagi M, Tanabe K et al. (2008) Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 26:101–106.

    Article  PubMed  CAS  Google Scholar 

  33. Yu J, Vodyanik MA, Smuga-Otto K et al. (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920.

    Article  PubMed  CAS  Google Scholar 

  34. Stadtfeld M, Nagaya M, Utikal J et al. (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949.

    Article  PubMed  CAS  Google Scholar 

  35. Okita K, Nakagawa M, Hyenjong H et al. (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949–953.

    Article  PubMed  CAS  Google Scholar 

  36. Wernig M, Zhao JP, Pruszak J et al. (2008) 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 105:5856–5861.

    Article  PubMed  CAS  Google Scholar 

  37. Minguez-Castellanos A, Escamilla-Sevilla F, Hotton GR et al. (2007) Carotid body autotransplantation in Parkinson disease: A clinical and PET study. J Neurol Neurosurg Psychiatry 78: 825–831.

    Article  PubMed  Google Scholar 

  38. Dezawa M, Hoshino M, Cho H et al. (2004) Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest 113:1701–1710.

    PubMed  CAS  Google Scholar 

  39. Borta A, Hoglinger GU (2007) Dopamine and adult neurogenesis. J Neurochem 100:587–595.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Our own work is supported by the Medical Research Council and Parkinson’s Disease Society.

Author information

Authors and Affiliations

  1. Brain Repair Centre, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK

    R. Laguna Goya & R.A. Barker

  2. Department of Neurology, Addenbrookes Hospital, CB2 2QQ, Cambridge, UK

    R.A. Barker

  3. Edith Cowan University, Perth, Australia

    R.A. Barker

Authors
  1. R. Laguna Goya
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  2. R.A. Barker
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Corresponding author

Correspondence to R. Laguna Goya .

Editor information

Editors and Affiliations

  1. Inst. Immunologie, Universität Witten/Herdecke, Stockumer Str. 10, Witten, 58448, Germany

    Thomas Dittmar

  2. Inst. Immunologie, Universität Witten/Herdecke, Stockumer Str. 10, Witten, 58448, Germany

    Kurt S. Zanker

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© 2009 Springer Science+Business Media B.V.

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Goya, R.L., Barker, R. (2009). Cell Therapy in Parkinson’s Disease. In: Dittmar, T., Zanker, K. (eds) Stem Cell Biology in Health and Disease. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3040-5_7

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