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Neural Stem Cells and Transplantation Studies in Parkinson’s Disease

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 741))

Abstract

Parkinson’s disease (PD), one of the most frequent neurodegenerative disorders, is primarily caused by the selective degeneration of specific neuronal populations, particularly dopaminergic neurons within the substantia nigra projecting to the striatum (nigrostriatal neurons). The current pharmacological treatments are efficient in the early stage of the disease but with the continuous use of the pro-dopaminergic medication may become less effective and cause motor complications. Cell therapy is an emergent alternative therapeutic strategy to PD and consists in the replacement of damaged neurons by new cells that could help to restore the nigrostriatal pathway. For this purpose, stem cells constitute a promising tool that could provide new sources of cells to be used for experimental transplantation studies in PD, as well as in other neurological disorders. Numerous studies are being made with the use of tissue specific neural progenitors obtained from either fetal or adult nervous systems. In this chapter we will summarize the numerous preclinical and clinical studies performed so far in animal models of the disease as well as in patients and how the use of neural stem cells might improve the current cell therapies.

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References

  1. Freed CR, Greene PE, Breeze RE et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. New Engl J Med 2001; 344:710–719.

    Article  PubMed  CAS  Google Scholar 

  2. Olanow CW, Goetz CG, Kordower JH et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 2003; 54:403–414.

    Article  PubMed  Google Scholar 

  3. Kriks S, Studer L. Protocols for generating ES cell-derived dopamine neurons. Adv Exp Med Biol 2009; 651:101–111.

    Article  PubMed  Google Scholar 

  4. Minguez-Castellanos A, Escamilla-Sevilla F. Cell therapy and other neuroregenerative strategies in Parkinson’s disease (I and II). Rev Neurologia 2005; 41:604–614, 684-693.

    CAS  Google Scholar 

  5. Lindvall O, Kokaia Z, Martinez-Serrano A. Stem cell therapy for human neurodegenerative disorders-how to make it work. Nat Med 2004; 10 Suppl:S42–S50.

    Article  PubMed  Google Scholar 

  6. Freed CR. Will embryonic stem cells be a useful source of dopamine neurons for transplant into patients with Parkinson’s disease? P Natl Acad Sci USA 2002; 99:1755–1757.

    Article  CAS  Google Scholar 

  7. Snyder BJ, Olanow CW. Stem cell treatment for Parkinson’s disease: an update for 2005. Curr Opin Neurol 2005; 18:376–385.

    Article  PubMed  CAS  Google Scholar 

  8. Altman J. Are new neurons formed in the brains of adult mammals? Science 1962; 135:1127–1128.

    Article  PubMed  CAS  Google Scholar 

  9. Eriksson PS, Perfilieva E, Bjork-Eriksson T et al. Neurogenesis in the adult human hippocampus. Nat Med 1998; 4:1313–1317.

    Article  PubMed  CAS  Google Scholar 

  10. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992; 255:1707–1710.

    Article  PubMed  CAS  Google Scholar 

  11. Kintner C. Neurogenesis in embryos and in adult neural stem cells. J Neurosci 2001; 22:639–643.

    Google Scholar 

  12. Doe CQ. Neural stem cells: balancing self-renewal with differentiation. Development 2008; 135:1575–1587.

    Article  PubMed  CAS  Google Scholar 

  13. Falk A, Frisen J. New neurons in old brains. Ann Med 2005; 37:480–486.

    Article  PubMed  Google Scholar 

  14. Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell 2008; 132:645–660.

    Article  PubMed  CAS  Google Scholar 

  15. Rietze RL, Reynolds BA. Neural stem cell isolation and characterization. Methods Enzymol 2006; 419:3–23.

    Article  PubMed  CAS  Google Scholar 

  16. Molofsky AV, Pardal R, Morrison SJ. Diverse mechanisms regulate stem cell self-renewal. Curr Opin Cell Biol 2004; 16:700–707.

    Article  PubMed  CAS  Google Scholar 

  17. Alvarez-Buylla A, Lim DA. For the long run: maintaining germinal niches in the adult brain. Neuron 2004; 41:683–686.

    Article  PubMed  CAS  Google Scholar 

  18. Mirzadeh Z, Merkle FT, Soriano-Navarro et al. Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 2008; 3:265–278.

    Article  PubMed  CAS  Google Scholar 

  19. Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 2000; 425:479–494.

    Article  PubMed  CAS  Google Scholar 

  20. Shen Q, Wang Y, Kokovay E et al. Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 2008; 3:289–300.

    Article  PubMed  CAS  Google Scholar 

  21. Tavazoie M, Van derVeken L, Silva-Vargas V et al. A specialized vascular niche for adult neural stem cells. Cell Stem Cell 2008; 3:279–288.

    Article  PubMed  CAS  Google Scholar 

  22. Carmeliet P. Blood vessels and nerves: common signals, pathways and diseases. Nat Rev Genet 2001; 4:710–720.

    Article  Google Scholar 

  23. Calof AL, Mumm JS, Rim PC et al. The neuronal stem cell of the olfactory epithelium. J Neurobiol 1998; 36:190–205.

    Article  PubMed  CAS  Google Scholar 

  24. Pardal R, Ortega-Saenz P, Duran R et al. Glia-like stem cells sustain physiologic neurogenesis in the adult mammalian carotid body. Cell 2007; 131:364–377.

    Article  PubMed  CAS  Google Scholar 

  25. Kruger GM, Mosher JT, Bixby S et al. Neural crest stem cells persist in the adult gut but undergo changes in self-renewal, neuronal subtype potential, and factor responsiveness. Neuron 2002; 35:657–669.

    Article  PubMed  CAS  Google Scholar 

  26. Tomita Y, Matsumura K, Wakamatsu Y et al. Cardiac neural crest cells contribute to the dormant multipotent stem cell in the mammalian heart. J Cell Biol 2005; 170:1135–1146.

    Article  PubMed  CAS  Google Scholar 

  27. Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci 1997; 17:5046–5061.

    PubMed  CAS  Google Scholar 

  28. Lois C, Alvarez-Buylla A. Long-distance neuronal migration in the adult mammalian brain. Science 1994; 264:1145–1148.

    Article  PubMed  CAS  Google Scholar 

  29. Doetsch F, Caille I, Lim DA et al. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 1999; 97:703–716.

    Article  PubMed  CAS  Google Scholar 

  30. Arenas E. Engineering a dopaminergic phenotype in stem/precursor cells: role of Nurr1, glia-derived signals and Wnts. Ann N Y Acad Sci 2005; 1049:51–66.

    Article  PubMed  CAS  Google Scholar 

  31. Seri B, Garcia-Verdugo JM, McEwen BS et al. Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 2001; 21:7153–7160.

    PubMed  CAS  Google Scholar 

  32. Arvidsson A, Collin T, Kirik D et al. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 2001; 8:963–970.

    Article  Google Scholar 

  33. Kuo CT, Mirzadeh Z, Soriano-Navarro M et al. Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Cell 2006; 127:1253–1264.

    Article  PubMed  CAS  Google Scholar 

  34. Schwarting RK, Huston JP. The unilateral 6-hydroxydopamine lesion model in behavioral brain research. Analysis of functional deficits, recovery and treatments. Prog Neurobiol 1996; 50:275–331.

    Article  PubMed  CAS  Google Scholar 

  35. Heikkila RE, Hess A, Duvoisin RC. Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine in mice. Science 1984; 224:1451–1453.

    Article  PubMed  CAS  Google Scholar 

  36. Li Y, Liu W, Oo TF et al. Mutant LRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson’s disease. Nature Neuroscience 2009; 12:826–828.

    Article  PubMed  CAS  Google Scholar 

  37. Pascual A, Hidalgo-Figueroa M, Piruat JI et al. Absolute requirement of GDNF for adult catecholaminergic neuron survival. Nature Neuroscience 2008; 11:755–761.

    Article  PubMed  CAS  Google Scholar 

  38. Kirik D, Georgievska B, Bjorklund A. Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nature Neuroscience 2004; 7:105–110.

    Article  PubMed  CAS  Google Scholar 

  39. Bjorklund A, Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 1979; 177:555–560.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  41. Redmond DE, Sladek JR Jr, Roth RH et al. Fetal neuronal grafts in monkeys given methylphenyltetrahydropyridine. Lancet 1986; 1:1125–1127.

    Article  PubMed  CAS  Google Scholar 

  42. Freed WJ, Morihisa JM, Spoor E et al. Transplanted adrenal chromaffin cells in rat brain reduce lesion-induced rotational behaviour. Nature 1981; 292:351–352.

    Article  PubMed  CAS  Google Scholar 

  43. Galpern WR, Burns LH, Deacon TW et al. Xenotransplantation of porcine fetal ventral mesencephalon in a rat model of Parkinson’s disease: functional recovery and graft morphology. Exp Neurol 1996; 140:1–13.

    Article  PubMed  CAS  Google Scholar 

  44. Nakao N, Kakishita K, Uematsu Y et al. Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease. J Neurosurg 2001; 95:275–284.

    Article  PubMed  CAS  Google Scholar 

  45. Espejo EF, Montoro RJ, Armengol JA et al. Cellular and functional recovery of Parkinsonian rats after intrastriatal transplantation of carotid body cell aggregates. Neuron 1998; 20:197–206.

    Article  PubMed  CAS  Google Scholar 

  46. Toledo-Aral JJ, Mendez-Ferrer S, Pardal R et al. Trophic restoration of the nigrostriatal dopaminergic pathway in long-term carotid body-grafted parkinsonian rats. J Neurosci 2003; 23:141–148.

    PubMed  CAS  Google Scholar 

  47. Luquin MR, Montoro RJ, Guillen J et al. Recovery of chronic parkinsonian monkeys by autotransplants of carotid body cell aggregates into putamen. Neuron 1999; 22:743–750.

    Article  PubMed  CAS  Google Scholar 

  48. Villadiego J, Mendez-Ferrer S, Valdes-Sanchez T et al. Selective glial cell line-derived neurotrophic factor production in adult dopaminergic carotid body cells in situ and after intrastriatal transplantation. J Neurosci 2005; 25:4091–4098.

    Article  PubMed  CAS  Google Scholar 

  49. Backlund EO, Granberg PO, Hamberger B et al. Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials. J Neurosurg 1985; 62:169–173.

    Article  PubMed  CAS  Google Scholar 

  50. Lindvall O, Rehncrona S, Brundin P et al. Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson’s disease. A detailed account of methodology and a 6-month follow-up. Arch Neurol 1989; 46:615–631.

    Article  PubMed  CAS  Google Scholar 

  51. Arjona V, Minguez-Castellanos A, Montoro RJ et al. Autotransplantation of human carotid body cell aggregates for treatment of Parkinson’s disease. Neurosurgery 2003; 53:321–328; discussion 328-330.

    Article  PubMed  Google Scholar 

  52. 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.

    Article  PubMed  CAS  Google Scholar 

  53. Kopyov OV, Jacques DS, Lieberman A et al. Outcome following intrastriatal fetal mesencephalic grafts for Parkinson’s patients is directly related to the volume of grafted tissue. Exp Neurol 1997; 146:536–545.

    Article  PubMed  CAS  Google Scholar 

  54. Minguez-Castellanos A, Escamilla-Sevilla F, Hotton GR et al. Carotid body autotransplantation in Parkinson disease: a clinical and positron emission tomography study. J Neurol Neurosur Ps 2007; 78:825–831.

    Article  Google Scholar 

  55. Kiskinis E, Eggan K. Progress toward the clinical application of patient-specific pluripotent stem cells. J Clin Invest 2010; 120:51–59.

    Article  PubMed  CAS  Google Scholar 

  56. Lindvall O, Kokaia Z. Prospects of stem cell therapy for replacing dopamine neurons in Parkinson’s disease. Trends Pharmacol Sci 2009; 30:260–267.

    Article  PubMed  CAS  Google Scholar 

  57. Perrier AL, Tabar V, Barberi T et al. Derivation of midbrain dopamine neurons from human embryonic stem cells. P Natl Acad Sci U S A 2004; 101:12543–12548.

    Article  CAS  Google Scholar 

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Correspondence to José López-Barneo .

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© 2012 Landes Bioscience and Springer Science+Business Media

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Pardal, R., López-Barneo, J. (2012). Neural Stem Cells and Transplantation Studies in Parkinson’s Disease. In: López-Larrea, C., López-Vázquez, A., Suárez-Álvarez, B. (eds) Stem Cell Transplantation. Advances in Experimental Medicine and Biology, vol 741. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-2098-9_14

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