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Regenerative Medicine and Cell Therapy pp 1–22Cite as

Cell Therapy for Neurodegenerative Disorders

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Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

Abstract

The last decade has seen tremendous progress in stem cell biology, targeted genome editing, bioengineering, and systems neuroscience supporting the notion that cell therapy of various disorders of the central nervous system (CNS) may become clinical reality in the near future. In particular, the advent of induced pluripotent stem (iPS) cells and access to large quantities of patient- and disease-specific cellular material offers unique opportunities for developmental biology and regenerative medicine. It is now possible to investigate the molecular underpinnings of monogenic and complex human diseases using stem cell-derived neural phenotypes. Molecular insights from such studies will leverage the development of diagnostic tools, biomarkers, drugs, and cell replacement with the ultimate goal to halt or reverse the course of devastating maladies. In this book chapter, I shall discuss the opportunities and emerging challenges of stem cell-based therapies and highlight common neurological diseases that may benefit from such iatrogenic interventions.

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References

  1. Bhardwaj RD, Curtis MA, Spalding KL, Buchholz BA, Fink D, Bjork-Eriksson T, Nordborg C, Gage FH, Druid H, Eriksson PS, Frisen J (2006) Neocortical neurogenesis in humans is restricted to development. Proc Natl Acad Sci USA 103:12564–12568

    PubMed  CAS  Google Scholar 

  2. Geerts H (2009) Of mice and men: bridging the translational disconnect in CNS drug discovery. CNS Drugs 23:915–926

    PubMed  CAS  Google Scholar 

  3. Dawson TM, Ko HS, Dawson VL (2010) Genetic animal models of Parkinson’s disease. Neuron 66:646–661

    PubMed  CAS  Google Scholar 

  4. Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13:1161–1169

    PubMed  CAS  Google Scholar 

  5. Ramaswamy S, McBride JL, Kordower JH (2007) Animal models of Huntington’s disease. ILAR J 48:356–373

    PubMed  CAS  Google Scholar 

  6. Trancikova A, Ramonet D, Moore DJ (2011) Genetic mouse models of neurodegenerative diseases. Prog Mol Biol Transl Sci 100:419–482

    PubMed  CAS  Google Scholar 

  7. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    PubMed  CAS  Google Scholar 

  8. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    PubMed  CAS  Google Scholar 

  9. Jain S, Heutink P (2010) From single genes to gene networks: high-throughput-high-content screening for neurological diseases. Neuron 68:207–217

    PubMed  CAS  Google Scholar 

  10. Singec I, Knoth R, Meyer RP, Maciaczyk J, Volk B, Nikkhah G, Frotscher M, Snyder EY (2006) Defining the actual sensitivity and specificity of the neurosphere assay in stem cell biology. Nat Methods 3:801–806

    PubMed  CAS  Google Scholar 

  11. Singec I, Quiñones-Hinojosa A (2008) Neurospheres. In: Gage FH, Kempermann G, Song H (eds) Adult neurogenesis, vol 52, Cold Spring Harbor Laboratory Press. doi: 10.1101/087969784.52.119

  12. Chen G, Gulbranson DR, Hou Z, Bolin JM, Ruotti V, Probasco MD, Smuga-Otto K, Howden SE, Diol NR, Propson NE, Wagner R, Lee GO, Antosiewicz-Bourget J, Teng JM, Thomson JA (2011) Chemically defined conditions for human iPSC derivation and culture. Nat Methods 8:424–429

    PubMed  CAS  Google Scholar 

  13. Ludwig TE, Levenstein ME, Jones JM, Berggren WT, Mitchen ER, Frane JL, Crandall LJ, Daigh CA, Conard KR, Piekarczyk MS, Llanas RA, Thomson JA (2006) Derivation of human embryonic stem cells in defined conditions. Nat Biotechnol 24:185–187

    PubMed  CAS  Google Scholar 

  14. Xu RH, Peck RM, Li DS, Feng X, Ludwig T, Thomson JA (2005) Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Methods 2:185–190

    PubMed  CAS  Google Scholar 

  15. Meissner A (2010) Epigenetic modifications in pluripotent and differentiated cells. Nat Biotech 28:1079–1088

    CAS  Google Scholar 

  16. Pera MF, Tam PP (2010) Extrinsic regulation of pluripotent stem cells. Nature 465:713–720

    PubMed  CAS  Google Scholar 

  17. Young RA (2011) Control of the embryonic stem cell state. Cell 144:940–954

    PubMed  CAS  Google Scholar 

  18. Byrne JA, Pedersen DA, Clepper LL, Nelson M, Sanger WG, Gokhale S, Wolf DP, Mitalipov SM (2007) Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature 450:497–502

    PubMed  CAS  Google Scholar 

  19. Cowan CA, Atienza J, Melton DA, Eggan K (2005) Nuclear reprogramming of somatic cells after fusion with human embryonic stem cell. Science 309:1369–1373

    PubMed  CAS  Google Scholar 

  20. Egli D, Rosains J, Birkhoff G, Eggan K (2007) Developmental reprogramming after chromosome transfer into mitotic mouse zygotes. Nature 447:679–685

    PubMed  CAS  Google Scholar 

  21. Hochedlinger K, Jaenisch R (2002) Monoclonal mice generated by nuclear transfer from mature B and T donor cells. Nature 415:1035–1038

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  23. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    PubMed  CAS  Google Scholar 

  24. Zhao XY, Li W, Lv Z, Liu L, Tong M, Hai T, Hao J, Guo CL, Ma QW, Wang L, Zeng F, Zhou Q (2009) iPS cells produce viable mice through tetraploid complementation. Nature 461:86–90

    PubMed  CAS  Google Scholar 

  25. Bock C, Kiskinis E, Verstappen G, Gu H, Boulting G, Smith ZD, Ziller M, Croft GF, Amoroso MW, Oakley DH, Gnirke A, Eggan K, Meissner A (2011) Reference Maps of human ES and iPS cell variation enable high-throughput characterization of pluripotent cell lines. Cell 144:439–452

    PubMed  CAS  Google Scholar 

  26. Zhao T, Zhang ZN, Rong Z, Xu Y (2011) Immunogenicity of induced pluripotent stem cell. Nature 474:212–215

    PubMed  CAS  Google Scholar 

  27. Gaulden J, Reiter JF (2008) Neur-ons and neur-offs: regulators of neural induction in vertebrate embryos and embryonic stem cells. Hum Mol Genet 17(R1):R60–66

    Google Scholar 

  28. Zhang SC, Wernig M, Duncan ID, Brüstle O, Thomson JA (2001) In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechol 19:1129–1133

    CAS  Google Scholar 

  29. Pruszak J, Sonntag KC, Aung MH, Sanchez-Pernaute R, Isacson O (2007) Markers and methods for cell sorting of human embryonic stem cell-derived neural cell populations. Stem Cells 25:2257–2268

    PubMed  Google Scholar 

  30. Perrier AL, Tabar V, Barberi T, Rubio ME, Bruses J, Topf N, Harrison NL, Studer L (2004) Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci USA 101:12543–12548

    PubMed  CAS  Google Scholar 

  31. Pera MF, Andrade J, Houssami S, Reubinoff B, Trounson A, Stanley EG, Ward-van Oostwaard D, Mummery C (2004) Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin. J Cell Sci 117:1269–1280

    PubMed  CAS  Google Scholar 

  32. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27:275–280

    PubMed  CAS  Google Scholar 

  33. Kriks S, Shim, JW, Piao J, Ganat YM, Wakeman DR, Xie Z, Carrillo-Reid L, Auyeung G, Antonacci C, Buch A, Yang L, Beal MF, Surmeier DJ, Kordower JH, Tabar V, Studer L (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480(7378):547–551 doi: 10.1038/nature10648

    Google Scholar 

  34. Smith JR, Vallier L, Lupo G, Alexander M, Harris WA, Pedersen RA (2008) Inhibition of activin/nodal signaling promotes specification of human embryonic stem cells into neuroectoderm. Dev Biol 313:107–117

    PubMed  CAS  Google Scholar 

  35. Sharp J, Hatch M, Nistor G, Keirstead H (2011) Derivation of oligodendrocyte progenitor cells from human embryonic stem cells. Methods Mol Biol 767:399–409

    PubMed  CAS  Google Scholar 

  36. Krencik R, Weick JP, Liu Y, Zhang ZJ, Zhang SC (2011) Specification of transplantable astroglial subtypes from human pluripotent stem cells. Nat Biotechnol 29:528–534

    PubMed  CAS  Google Scholar 

  37. Scadden DT (2006) The stem-cell niche as an entity of action. Nature 441:1075–1079

    PubMed  CAS  Google Scholar 

  38. Vunjak-Novakovic G, Scadden DT (2011) Biomimetic platforms for human stem cell research. Cell Stem Cell 8:252–261

    PubMed  CAS  Google Scholar 

  39. Gobaa S, Hoehnel S, Roccio M, Negro A, Kobel S, Lutolf MP (2011) Artificial niche microarrays for probing single stem cell fate in high throughput. Nat Methods 8:949–955

    PubMed  CAS  Google Scholar 

  40. Park KI, Teng YD, Snyder EY (2002) The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nat Biotechnol 20:1111–1117

    PubMed  CAS  Google Scholar 

  41. Carvajal-Vergara X, Sevilla A, D’Souza SL, Ang YS, Schaniel C, Lee DF, Yang L, Kaplan AD, Adler ED, Rozov R, Ge Y, Cohen N, Edelmann LJ, Chang B, Waghray A, Su J, Pardo S, Lichtenbelt KD, Tartaglia M, Gelb BD, Lemischka IR (2010) Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 465:808–812

    PubMed  CAS  Google Scholar 

  42. Ebert AD, Yu J, Rose FF Jr, Mattis VB, Lorson CL, Thomson JA, Svendsen CN (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457:277–280

    PubMed  CAS  Google Scholar 

  43. Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, Ganat YM, Menon J, Shimizu F, Viale A, Tabar V, Sadelain M, Studer L (2009) Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461:402–406

    PubMed  CAS  Google Scholar 

  44. Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, Panopoulos AD, Suzuki K, Kurian L, Walsh C, Thompson J, Boue S, Fung HL, Sancho-Martinez I, Zhang K, Yates J 3rd (2011) Izpisua Belmonte, J.C.: Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472:221–225

    PubMed  CAS  Google Scholar 

  45. Yazawa M, Hsueh B, Jia X, Pasca AM, Bernstein JA, Hallmayer J, Dolmetsch RE (2011) Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome. Nature 471:230–234

    PubMed  CAS  Google Scholar 

  46. Hockemeyer D, Jaenisch R (2010) Gene targeting in human pluripotent cells. Cold Spring Harb Symp Quant Biol 75:201–209

    PubMed  CAS  Google Scholar 

  47. Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ, Zhang L, Santiago Y, Miller JC, Zeitler B, Cherone JM, Meng X, Hinkley SJ, Rebar EJ, Gregory PD, Urnov FD, Jaenisch R (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29:731–734

    PubMed  CAS  Google Scholar 

  48. Soldner F, Laganière J, Cheng AW, Hockemeyer D, Gao Q, Alagappan R, Khurana V, Golbe LI, Myers RH, Lindquist S, Zhang L, Guschin D, Fong LK, Vu BJ, Meng X, Urnov FD, Rebar EJ, Gregory PD, Zhang HS, Jaenisch R (2011) Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations. Cell 146:318–331

    PubMed  CAS  Google Scholar 

  49. Nguyen HN, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P, Kee P, Schule B, Dolmetsch RE, Langston W, Palmer TD, Pera RR (2011) LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8:267–280

    PubMed  CAS  Google Scholar 

  50. Saha K, Jaenisch R (2009) Technical challenges in using human induced pluripotent stem cells to model disease. Cell Stem Cell 5:584–595

    PubMed  CAS  Google Scholar 

  51. Renfranz PJ, Cunningham MG, McKay RD (1991) Region-specific differentiation of the hippocampal stem cell line HiB5 upon implantation into the developing mammalian brain. Cell 66:713–729

    PubMed  CAS  Google Scholar 

  52. Flax JD, Aurora S, Yang C, Simonin C, Wills AM, Billinghurst LL, Jendoubi M, Sidman RL, Wolfe JH, Kim SU, Snyder EY (1998) Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat Biotechnol 16:1033–1039

    PubMed  CAS  Google Scholar 

  53. Englund U, Bjorklund A, Wictorin K, Lindvall O, Kokaia M (2002) Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry. Proc Natl Acad Sci USA 99:17089–17094

    PubMed  CAS  Google Scholar 

  54. Lee JP, Jeyakumar M, Gonzalez R, Takahashi H, Lee PJ, Baek RC, Clark D, Rose H, Fu G, Clarke J, McKercher S, Meerloo J, Muller FJ, Park KI, Butters TD, Dwek RA, Schwartz P, Tong G, Wenger D, Lipton SA, Seyfried TN, Platt FM, Snyder EY (2007) Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nat Med 13:439–447

    PubMed  CAS  Google Scholar 

  55. Windrem MS, Schanz SJ, Guo M, Tian GF, Washco V, Stanwood N, Rasband M, Roy NS, Nedergaard M, Havton LA, Wang S, Goldman SA (2008) Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse. Cell Stem Cell 2:553–565

    PubMed  CAS  Google Scholar 

  56. Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, Small JE, Herrlinger U, Ourednik V, Black PM, Breakefield XO, Sndyer EY (2000) Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci USA 97:12846–12851

    PubMed  CAS  Google Scholar 

  57. Glass R, Synowitz M, Kronenberg G, Walzlein JH, Markovic DS, Wang LP, Gast D, Kiwit J, Kempermann G, Kettenmann H (2005) Glioblastoma-induced attraction of endogenous neural precursor cells is associated with improved survival. J Neurosci 25:2637–2646

    PubMed  CAS  Google Scholar 

  58. Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101:18117–18122

    PubMed  CAS  Google Scholar 

  59. Tamaki SJ, Jacobs Y, Dohse M, Capela A, Cooper JD, Reitsma M, He D, Tushinski R, Belichenko PV, Salehi A, Mobley W, Gage FH, Huhn S, Tsukamoto AS, Weissman IL, Uchida N (2009) Neuroprotection of host cells by human central nervous system stem cells in a mouse model of infantile neuronal ceroid lipofuscinosis. Cell Stem Cell 5:310–319

    PubMed  CAS  Google Scholar 

  60. Jandial R, Singec I, Ames CP, Snyder EY (2008) Genetic modification of neural stem cells. Mol Ther 16:450–457

    PubMed  CAS  Google Scholar 

  61. Aboody K, Capela A, Niazi N, Stern JH, Temple S (2011) Translating stem cell studies to the clinic for CNS repair: current state of the art and the need for a Rosetta Stone. Neuron 70:597–613

    PubMed  CAS  Google Scholar 

  62. Nikkhah G, Falkenstein G, Rosenthal C (2001) Restorative plasticity of dopamine neuronal transplants depends on the degree of hemispheric dominance. J Neurosci 21:6252–6263

    PubMed  CAS  Google Scholar 

  63. Alterman RL, Tagliati M, Olanow CW (2011) Open-label surgical trials for Parkinson disease: time for reconsideration. Ann Neurol 70:5–8

    PubMed  Google Scholar 

  64. Roy NS, Cleren C, Singh SK, Yang L, Beal MF, Goldman SA (2006) Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat Med 12:1259–1268

    PubMed  CAS  Google Scholar 

  65. Lane EL, Björklund A, Dunnett SB, Winkler C (2010) Neural grafting in Parkinson’s disease unraveling the mechanisms underlying graft-induced dyskinesia. Prog Brain Res 184:295–309

    PubMed  Google Scholar 

  66. Barker RA, Kuan WL (2010) Graft-induced dyskinesias in Parkinson’s disease: what is it all about? Cell Stem Cell 7:148–149

    PubMed  CAS  Google Scholar 

  67. Lindvall O, Björklund A (2011) Cell therapeutics in Parkinson’s disease. Neurotherapeutics 8:539–548

    PubMed  Google Scholar 

  68. Steiner B, Winter C, Blumensath S, Paul G, Harnack D, Nikkhah G, Kupsch A (2008) Survival and functional recovery of transplanted human dopaminergic neurons into hemiparkinsonian rats depend on the cannula size of the implantation instrument. J Neurosci Methods 169:128–134

    PubMed  Google Scholar 

  69. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH (2010) Mechanisms underlying inflammation in neurodegeneration. Cell 140:918–934

    PubMed  CAS  Google Scholar 

  70. Hansen C, Angot E, Bergström AL, Steiner JA, Pieri L, Paul G, Outeiro TF, Melki R, Kallunki P, Fog K, Li JY, Brundin P (2011) α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells. J Clin Invest 121:715–725

    PubMed  CAS  Google Scholar 

  71. Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW (2008) Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med 14:504–506

    PubMed  CAS  Google Scholar 

  72. Mendez I, Viñuela A, Astradsson A, Mukhida K, Hallet P, Robertson H, Tierney T, Holness R, Dagher A, Trojanowski JQ, Isacson O (2008) Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years. Nat Med 14:507–509

    PubMed  CAS  Google Scholar 

  73. Berridge MJ (2010) Calcium hypothesis of Alzheimer’s disease. Pflugers Arch 459:441–449

    PubMed  CAS  Google Scholar 

  74. Nakamura T, Lipton SA (2010) Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer’s and Parkinson’s diseases. Apoptosis 15:1354–1363

    PubMed  CAS  Google Scholar 

  75. Sulzer D (2007) Multiple hit hypothesis for dopamine neuron loss in Parkinson’s disease. Trends Neurosci 30:244–250

    PubMed  CAS  Google Scholar 

  76. Lunn JS, Sakowski SA, Hur J, Feldman EL (2011) Stem cell technology for neurodegenerative diseases. Ann Neurol 70:353–361

    PubMed  CAS  Google Scholar 

  77. Lott IT, Head E (2005) Alzheimer disease and Down syndrome: factors in pathogenesis. Neurobiol Aging 26:383–389

    PubMed  CAS  Google Scholar 

  78. Knoth R, Singec I, Ditter M, Pantazis G, Capetian P, Meyer RP, Horvat V, Volk B, Kempermann G (2010) Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS ONE 5:e8809

    PubMed  Google Scholar 

  79. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van Praag H (2010) When neurogenesis encounters aging and disease. Trends Neurosci 33:569–579

    PubMed  CAS  Google Scholar 

  80. Nagahara AH, Tuszynski MH (2011) Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 10:209–219

    PubMed  CAS  Google Scholar 

  81. Singec I, Jandial R, Crain A, Nikkhah G, Snyder EY (2007) The leading edge of stem cell therapeutics. Annu Rev Med 58:313–328

    PubMed  CAS  Google Scholar 

  82. Tuszynski MH, Thal L, Pay M, Salmon DP, Salmon DP, U HS, Bakay R, Patel P, Blesch A, Vahlsing HL, Ho G, Tong G, Potkin SG, Fallon J, Hansen L, Mufson EJ, Kordower JH, Gall C, Conner J (2005) A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 11:551–555

    PubMed  CAS  Google Scholar 

  83. Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ (2008) Disease-specific induced pluripotent stem cells. Cell 134:877–886

    PubMed  CAS  Google Scholar 

  84. Berninger B, Costa MR, Koch U, Schroeder T, Sutor B, Grothe B, Götz M (2007) Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia. J Neurosci 27:8654–8664

    PubMed  CAS  Google Scholar 

  85. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Südhof TC, Wernig M (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463:1035–1041

    PubMed  CAS  Google Scholar 

  86. Qiang L, Fujita R, Yamashita T, Angulo S, Rhinn H, Rhee D, Doege C, Chau L, Aubry L, Vanti WB, Moreno H, Abeliovich A (2011) Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell 146:359–371

    PubMed  CAS  Google Scholar 

  87. Joers VL, Emborg ME (2009) Preclinical assessment of stem cell therapies for neurological diseases. ILAR J 51:24–41

    PubMed  Google Scholar 

  88. Björklund A, Dunnett SB (2007) Dopamine neuron systems in the brain: an update. Trends Neurosci 30:194–202

    PubMed  Google Scholar 

  89. Braak H, Del Tredici K (2009) Neuroanatomy and pathology of sporadic Parkinson’s disease. Adv Anat Embryol Cell Biol 201:1–119

    PubMed  Google Scholar 

  90. Halliday G, Lees A, Stern M (2011) Milestones in Parkinson’s disease—clinical and pathological features. Mov Disord 26:1015–1021

    PubMed  Google Scholar 

  91. Vesper J, Haak S, Ostertag C, Nikkhah G (2007) Subthalamic nucleus deep brain stimulation in elderly patients–analysis of outcome and complications. BMC Neurol 7:7

    PubMed  Google Scholar 

  92. Iravani MM, Jenner P (2011) Mechanisms underlying the onset and expression of levodopa-induced dyskinesia and their pharmacological manipulation. J Neural Transm 118:1661–1690

    PubMed  CAS  Google Scholar 

  93. Kim JH, Auerbach JM, Rodríguez-Gómez JA, Velasco I, Gavin D, Lumelsky N, Lee SH, Nguyen J, Sánchez-Pernaute R, Bankiewicz K, McKay R (2002) Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature 418:50–56

    PubMed  CAS  Google Scholar 

  94. Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, Yow A, Soldner F, Hockemeyer D, Hallet PJ, Osborn T, Jaenisch R, Isacson O (2010) Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci USA 107:15921–15926

    PubMed  CAS  Google Scholar 

  95. Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R (2009) Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136:964–977

    PubMed  CAS  Google Scholar 

  96. Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R (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

    PubMed  CAS  Google Scholar 

  97. Caiazzo M, 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 (2011) Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature 476:224–227

    PubMed  CAS  Google Scholar 

  98. Pfisterer U, Kirkeby A, Torper O, Wood J, Nelander J, Dufour A, Björklund A, Lindvall O, Jacobsson J, Parmar M (2011) Direct conversion of human fibroblasts to dopaminergic neurons. Proc Natl Acad Sci USA 108:10343–10348

    PubMed  CAS  Google Scholar 

  99. Benraiss A, Goldman SA (2011) Cellular therapy and induced neuronal replacement for Huntington’s disease. Neurotherapeutics 8:577–590

    PubMed  CAS  Google Scholar 

  100. Zuccato C, Cattaneo E (2009) Brain-derived neurotrophic factor in neurodegenerative diseases. Nat Rev Neurol 5:311–322

    PubMed  CAS  Google Scholar 

  101. Dunnett SB, Rosser AE (2011) Cell-based treatments for huntington’s disease. Int Rev Neurobiol 98:483–508

    PubMed  Google Scholar 

  102. Nicoleau C, Viegas P, Peschanski M, Perrier AL (2011) Human pluripotent stem cell therapy for Huntington’s disease: technical, immunological, and safety challenges. Neurotherapeutics 8:562–576

    PubMed  Google Scholar 

  103. Bachoud-Lévi AC, Gaura V, Brugières P, Lefaucheur JP, Boissé MF, Maison P, Baudic S, Ribeiro MJ, Bourdet C, Remy P, Cesaro P, Hantraye P, Peschanski M (2006) Effect of fetal neural transplants in patients with Huntington’s disease 6 years after surgery: a long-term follow-up study. Lancet Neurol 5:303–309

    PubMed  Google Scholar 

  104. Capetian P, Knoth R, Maciaczyk J, Pantazis G, Ditter M, Bokla L, Landwehrmeyer GB, Volk B, Nikkhah G (2009) Histological findings on fetal striatal grafts in a Huntington’s disease patient early after transplantation. Neuroscience 160:661–675

    PubMed  CAS  Google Scholar 

  105. Ferraiuolo L, Kirby J, Grierson AJ, Sendtner M, Shaw PJ (2011) Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis. Nat Rev Neurol 7:616–630

    PubMed  CAS  Google Scholar 

  106. Ilieva H, Polymenidou M, Cleveland DW (2009) Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol 187:761–772

    PubMed  CAS  Google Scholar 

  107. Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K (2007) Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model. Nat Neurosci 10:608–614

    PubMed  Google Scholar 

  108. Haidet-Phillips AM, Hester ME, Miranda CJ, Meyer K, Braun L, Frakes A, Song S, Likhite S, Murtha MJ, Foust KD, Rao M, Eagle A, Kammesheidt A, Christensen A, Mendell JR, Burghes AH, Kaspar BK (2011) Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol 29:824–828

    PubMed  CAS  Google Scholar 

  109. Marchetto MC, Muotri AR, Mu Y, Smith AM, Cezar GG, Gage FH (2008) Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells. Cell Stem Cell 3:649–657

    PubMed  CAS  Google Scholar 

  110. Peljto M, Dasen JS, Mazzoni EO, Jessell TM, Wichterle H (2010) Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation. Cell Stem Cell 7:355–366

    PubMed  CAS  Google Scholar 

  111. Wichterle H, Lieberam I, Porter JA, Jessell TM (2002) Directed differentiation of embryonic stem cells into motor neurons. Cell 110:385–397

    PubMed  CAS  Google Scholar 

  112. Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan K (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321:1218–1221

    PubMed  CAS  Google Scholar 

  113. Son EY, Ichida JK, Wainger BJ, Toma JS, Rafuse VF, Woolf CJ, Eggan K (2011) Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 9:205–218

    PubMed  CAS  Google Scholar 

  114. Schwab ME (2010) Functions of Nogo proteins and their receptors in the nervous system. Nat Rev Neurosci 11:799–811

    PubMed  CAS  Google Scholar 

  115. Deshpande DM, Kim YS, Martinez T, Carmen J, Dike S, Shats I, Rubin LL, Drummond J, Krishnan C, Hoke A, Maragakis N, Shefner J, Rothstein JD, Kerr DA (2006) Recovery from paralysis in adult rats using embryonic stem cells. Ann Neurol 60:32–44

    PubMed  CAS  Google Scholar 

  116. Gaillard A, Prestoz L, Dumartin B, Cantereau A, Morel F, Roger M, Jaber M (2007) Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons. Nat Neurosci 10:1294–1299

    PubMed  CAS  Google Scholar 

  117. Singec I, Snyder EY (2007) Quo vadis brain repair? A long axonal journey in the adult CNS. Cell Stem Cell 1:355–356

    PubMed  CAS  Google Scholar 

  118. Gowing G, Svendsen CN (2011) Stem cell transplantation for motor neuron disease: current approaches and future perspectives. Neurotherapeutics 8:591–606

    PubMed  Google Scholar 

  119. Eiraku M, Takata N, Ishibashi H, Kawada M, Sakakura E, Okuda S, Sekiguchi K, Adachi T, Sasai Y (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472:51–56

    PubMed  CAS  Google Scholar 

  120. Idelson M, Alper R, Obolensky A, Ben-Shushan E, Hemo I, Yachimovich-Cohen N, Khaner H, Smith Y, Wiser O, Gropp M, Cohen MA, Even-Ram S, Berman-Zaken Y, Matzrafi L, Rechavi G, Banin E, Reubinoff B (2009) Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells. Cell Stem Cell 5:396–408

    PubMed  CAS  Google Scholar 

  121. Marchetti V, Krohne TU, Friedlander DF, Friedlander M (2010) Stemming vision loss with stem cells. J Clin Investi 120:3012–3021

    CAS  Google Scholar 

  122. Meyer JS, Shearer RL, Capowski EE, Wright LS, Wallace KA, McMillan EL, Zhang SC, Gamm DM (2009) Modeling early retinal development with human embryonic and induced pluripotent stem cells. Proc Natl Acad Sci USA 106:16698–16703

    PubMed  CAS  Google Scholar 

  123. Osakada F, Ikeda H, Sasai Y, Takahashi M (2009) Stepwise differentiation of pluripotent stem cells into retinal cells. Nat Protoc 4:811–824

    PubMed  CAS  Google Scholar 

  124. Reh TA, Lamba D, Gust J (2010) Directing human embryonic stem cells to a retinal fate. Methods Mol Biol 636:139–153

    PubMed  CAS  Google Scholar 

  125. Wong IY, Poon MW, Pang RT, Lian Q, Wong D (2011) Promises of stem cell therapy for retinal degenerative diseases. Graefes Arch Clin Exp Opthalmol 249:1439–1448

    Google Scholar 

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Acknowledgments

I.S. was a fellow of the California Institute for Regenerative Medicine (CIRM) and was supported by the International Bipolar Foundation.

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  1. Ilyas Singec

    Present address: Pfizer Neuroscience, 700 Main Street, Cambridge, MA 02139, USA

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  1. Sanford-Burnham Medical Research Institute, La Jolla, CA, USA

    Ilyas Singec

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Correspondence to Ilyas Singec .

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  1. Royan Institute, Department of Developmental Biology, University of Science and Culture, PO Box 19395-4644, Tehran, Iran

    Hossein Baharvand

  2. , Regenerative Medicine, Royan Institute for Stem Cell Biology an, P.O. Box: 19395-4644, Tehran, Iran

    Nasser Aghdami

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Singec, I. (2013). Cell Therapy for Neurodegenerative Disorders . In: Baharvand, H., Aghdami, N. (eds) Regenerative Medicine and Cell Therapy. Stem Cell Biology and Regenerative Medicine. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-098-4_1

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