Cell-based therapies for Parkinson's disease: Past, present, and future

Antioxidants and Redox Signaling

Volumn 11, Issue 9, 2009, Pages 2189-2208

  Fitzpatrick, Kathleen M ^a   Raschke, James ^a   Emborg, Marina E ^a,b  

^a UNIVERSITY OF WISCONSIN   (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; 6 FLUORODOPA F 18; CYCLOSPORIN A; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; LEVODOPA; SOMATOMEDIN C;

AUTOTRANSPLANTATION; BRAIN DEPTH STIMULATION; BRAIN TRANSPLANTATION; CELL LOSS; CELL THERAPY; DOPAMINERGIC NERVE CELL; GENE MUTATION; GENE THERAPY; GENE TRANSFER; GRAFT SURVIVAL; GRAFT VERSUS HOST REACTION; HUMAN; NERVE DEGENERATION; NEURAL STEM CELL; NEUROTOXICITY; NONHUMAN; PARKINSON DISEASE; PIGMENT EPITHELIUM; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REVIEW; SYMPATHETIC NERVE CELL; XENOGRAFT;

ANIMALS; BRAIN; CELL TRANSPLANTATION; GENE THERAPY; HUMANS; PARKINSON DISEASE;

ANIMALIA;

EID: 68949217301     PISSN: 15230864     EISSN: None     Source Type: Journal    
DOI: 10.1089/ars.2009.2654     Document Type: Review

References (183)

1. Altman J and Das GD. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124: 319-335, 1965.
2. Andersson E, Tryggvason U, Deng Q, Friling S, Alekseenko Z, Robert B, Perlmann T, and Ericson J. Identification of intrinsic determinants of midbrain dopamine neurons. Cell 124: 393-405, 2006.
3. Annett LE, Dunnett SB, Martel FL, Rogers DC, Ridley RM, Baker HF, and Marsden CD. A functional assessment of embryonic dopaminergic grafts in the marmoset. Prog Brain Res 82: 535-542, 1990.
4. Annett LE, Martel FL, Rogers DC, Ridley RM, Baker HF, and Dunnett SB. Behavioral assessment of the effects of embryonic nigral grafts in marmosets with unilateral 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 125: 228-246, 1994.
5. Annett LE, Reading PJ, Tharumaratnam D, Abrous DN, Torres EM, and Dunnett SB. Conditioning versus priming of dopaminergic grafts by amphetamine. Exp Brain Res 93: 46-54, 1994.
6. Arjona V, Mínguez-Castellanos A, Montoro RJ, Ortega A, Escamilla F, Toledo-Aral JJ, Pardal R, Méndez-Ferrer S, Martín JM, Pérez M, Katati MJ, Valencia E, García T, and López-Barneo J. Autotransplantation of human carotid body cell aggregates for treatment of Parkinson's disease. Clinical Studies 53: 321-330, 2003.
7. Bakay RA, Barrow DL, Fiandaca MS, Iuvone PM, Schiff A, and Collins DC. Biochemical and behavioral correction of MPTP parkinson-like syndrome by fetal cell transplantation. Ann Y Acad Sci 495: 623-640, 1987.
8. Bakay RA, Fiandaca MS, Barrow DL, Schiff A, and Collins DC. Preliminary report on the use of fetal tissue transplantation to correct MPTP-induced parkinsonian-like syndrome in primates. Appl Neurophysiol 48: 358-361, 1985.
9. Bakay RA, Raiser CD, Stover NP, Subramian T, Cornfeldt ML, Schweikert AW, Allen RC, and Watts R. Implantation of Spheramine in advanced Parkinson's disease (PD). Front Biosci 9: 592-602, 2004.
10. Bankiewicz KS, Bringas J, Pivirotto P, Kutzscher E, Nagy D, and Emborg ME. Technique for bilateral intracranial implantation of cells in monkeys using an automated delivery system. Cell Transplant 9: 595-607, 2000.
11. Bankiewicz KS, Plunkett RJ, Jacobowitz DM, Porrino L, di Porzio U, London WT, Kopin IJ, and Oldfield EH. The effect of fetal mesencephalon implants on primate MPTP-induced parkinsonism: histochemical and behavioral studies. J Neurosurg 72: 231-244, 1990.
12. Bankiewicz KS, Plunkett RJ, Kophin IJ, Jacobwitz DM, London WT, and Oldfield EH. Transient behavioral recovery in hemiparkinsonian primates after adrenal medullary allografts. Prog Brain Res 78: 543-549, 1988.
13. Bankiewicz KS, Plunkett RJ, Mefford I, Kopin IJ, and Oldfield EH. Behavioral recovery from MPTP-induced parkinsonism in monkeys after intracerebral tissue implants is not related to CSF concentrations of dopamine metabolites. Prog Brain Res 82: 561-571, 1990.
14. Behrstock S, Ebert A, McHugh J, Vosberg S, Moore J, Schneider B, Capowski E, Hei D, Kordower J, Aebischer P, and Svendsen CN. Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonism rodents and aged primates. Gene Ther 13: 379-388, 2006.
15. Ben-Hur T, Idelson M, Khaner H, Pera M, Reinhartz E, Itzik A, and Reubinoff BE. Transplantation of human embryonic stem cell-derived neural progenitors improves behavioral deficit in Parkinsonian Rats. Stem Cells 22: 1246-1255, 2004.
16. Bezard E, Brotchie JM, and Gross CE. Pathophysiology of levodopa-induced dyskinesia: potential for new therapies. Nat Rev Neurosci 2: 577-588, 2001.
17. Birkmayer W and Hornykiewicz O. Der 1-3,4 Dioxyphenylalanin (D-dopa)-Effekt bei der Parkinson-Akinese. Wein Klin Wochenschr 73: 787-788, 1961.
18. Bjorklund A and Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by Intracerebral nigral transplants. Brain Res 177: 555-560, 1979.
19. Bjugstad KB, Redmond DE, Teng YD, Elsworth JD, Roth RH, Blanchard BC, Snyder EY, and Sladek JR Jr. Neural stem cells implanted into MPTP-treated monkeys increase the size of endogenous tyrosine hydroxylase-positive cells found in the striatum: a return to control measures. Cell Trans 14: 183-192, 2005.
20. Bjugstad KB, Teng YD, Redmond DE, Elsworth JD, Roth RH, Cornelius SK, Snyder EY, and Sladek JR. Human neural stem cells migrate along the nigrostriatal pathway in a primate model of Parkinson's disease. Exp Neurol 211: 362-369, 2008.
21. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, and Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24: 197-211, 2003.
22. Brundin P, Li JY, Holton JL, Lindvall O, and Revesz T. Research in motion: the enigma of Parkinson's disease pathology spread. Nature Reviews Neurosci 9: 741-745, 2008.
23. Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, and Kopin IJ. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6- tetrahydropyridine. Proc Natl Acad Sci USA 80: 4546-4550, 1983.
24. Buytaert-Hoefen KA, Alvarez E, and Freed CR. Generation of tyrosine hydroxylase positive neurons from human embryonic stem cells after coculture with cellular substrates and exposure to GDNF. Stem Cells 22: 669-674, 2004.
25. Buzanska L, Machaj EK, Zablocka B, Pojda Z, and Domanska-Janik K. Human cord blood-derived cells attain neuronal and glial features in vitro. J Cell Sci 115: 2131-2138, 2002.
26. Cai J, Donaldson A, Yang M, German MS, Enikolopov G, and Iacovitti L. The role of Lmx1a in the differentiation of human embryonic stem cells into midbrain dopamine neurons in culture and after transplantation into a Parkinson's disease model. Stem Cells 27: 220-229, 2009.
27. Cameron HA and Gould E. Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 61: 203-209, 1994.
28. Capitanio JP and Emborg ME. Contributions of nonhuman primates to neuroscience research. Lancet 371: 1126-1135, 2008.
29. Carlsson T, Winkler C, Lundblad M, Cenci MA, and Kirik D. Graft replacement and uneven pattern of reinnervation in the striatum is important for development of graft-induced dyskinesia. Neurobiol Dis 21: 657-668, 2006.
30. Carta M, Carlsson T, Munoz A, Kirik D, and Bjorklund A. Serotonin-dopamine interaction in the induction and maintenance of L-DOPA-induced dyskinesias. Prog Brain Res 172: 465-478, 2008.
31. Chamberlain SJ, Li XJ, and Lalande M. Induced pluripotent stem (iPS) cells as in vitro models of human neurogenetic disorders. Neurogenetics 9: 227-235, 2008.
32. Chung S, Shin B-S, Hwang M, Lardaro T, Kang UJ, Isacson O, and Kim K-S. Neural precursors derived from embryonic stem cells, but not those from fetal ventral mesencephalon, maintain the potential to differentiate into dopaminergic neurons after expansion in vitro. Stem Cells 24: 1583-1593, 2006.
33. Cohen J. New fight over fetal tissue grafts. Science 263: 600-601, 1994.
34. Collier TJ, Elsworth JD, Taylor JR, Sladek JR Jr, Roth RH, and Redmond DE Jr. Peripheral nerve-dopamine neuron co-grafts in MPTP-treated monkeys: Augmentation of tyrosine hydroxylase-positive fiber staining and dopamine content in host systems. Neurosci 61: 875-889, 1994.
35. Collier TJ, Redmond DE Jr, Sladek CD, Gallagher MJ, Roth RH, and Sladek JR Jr. Intracerebral grafting and culture of cryopreserved primate dopamine neurons. Brain Res 436: 363-366, 1987.
36. Collier TJ, Sortwell CE, Elsworth JD, Taylor JR, Roth RH, Sladek JR Jr, and Redmond DE Jr. Embryonic fetal mesencephalic grafts to the substantia nigra of MPTP-treated monkeys: feasibility relevant to multiple-target grafting as a therapy for Parkinson's disease. J Comp Neurol 21: 320-330, 2002.
37. Davis GC, Williams AC, and Markey SP. Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res 1: 249-254, 1979.
38. Defer GL, Geny C, Ricolfi F, Fenelon G, Monfort JC, Remy P, Villafane G, Jeny R, Samson Y, Keravel Y, Gaston A, Degos JD, Peschanski M, Cesaro P, and Nguyen JP. Long-term outcome of unilaterally transplanted parkinsonian patients: I. Clinical approach. Brain 119: 41-50, 1996.
39. Di Fonzo A, Rohe CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N, Goldwurm S, Breedveld G, Sampaio C, Meco G, Barbosa E, Oostra BA, Bonifati V; Italian Parkinson Genetics Network. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet 365: 412-415, 2005.
40. Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, and Eggan K. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321: 1218-1221, 2008.
41. Dismore JH, Manhart C, Raineri R Jacoby DB, and Moore A. No evidence for infection of human cells with porcine endogenous retrovirus (PERV) after exposure to porcine fetal neuronal cells. Transplantation 70: 1382-1389, 2000.
42. Doudet DJ, Cornfeldt ML, Honey CR, Schweikert AW, and Allen RC. PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson's disease. Exp Neurol 189: 361-368, 2004.
43. Dubach M, Schmidt RH, Martin R, German DC, and Bowden DM. Transplant improves hemiparkinsonian syndrome in nonhuman primate: Intracerebral injection, rotometry, tyrosine hydroxylase immunohistochemistry. Prog Brain Res 78: 491-496, 1988.
44. Dunn EH. Primary and secondary findings in a series of attempts to transplant cerebral cortex in the albino rat. J Comp Neurol 27: 565-582, 1917.
45. Ebert AD, Beres AJ, Barber AE, and Svendson CN. Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson's disease. Exp Neurol 209: 213-223, 2008.
46. Ehringer H, Hornykiewicz O. Verteilung von Noradrenalin und Dopamin (3-hydroxytyramin) im Gerhirn des Menschens und ihr Verhalten bei Erkrankugen des extrapyramidalen Systems. Klin Wochenschr 38: 1236-1239, 1960.
47. Elsworth JD, al-Tikriti MS, Sladek JR Jr, Taylor JR, Innis RB, Redmond DE Jr, and Roth RH. Novel radioligands for the dopamine transporter demonstrate the presence of intrastriatal nigral grafts in the MPTP-treated monkey: correlation with improved behavioral function. Exp Neurol 126: 300-304, 1994.
48. Emborg ME, Ebert AD, Moirano J, Peng S, Suzuki M, Capowski E, Joers V, Roitberg BZ, Aebischer P, and Svendsen CN. GDNF-secreting human neural progenitor cells increase tyrosine hydroxylase and VMAT2 expression in MPTP-treated cynomolgusmoneys. Cell Transplant 17: 383-395, 2008.
49. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nodborg C, Peterson DA, and Gage FH. Neurogensis in the adult human hippocampus. Nat Med 4: 1313-1317, 1998.
50. Fallahi-Sichani M, Soleimani M, Najafi SMA, Kiani J, Arefian E, and Atashi A. In vitro differentiation of cord blood unrestricted somatic stem cells expressing-associated genes into neuron-like cells. Cell Bio Intl 31: 299-307, 2007.
51. Feigin A and Eidelberg D. Gene transfer therapy for neurodegenerative disorders. Mov Disord 22: 1223-1228, 2007.
52. Fiandaca M, Forsayeth J, and Bankiewicz K. Current status of gene therapy trials for Parkinson's disease. Exp Neurol 209: 51-57, 2008.
53. Fiandaca MS, Kordower JH, Hansen JT, Jiao SS, and Gash DM. Adrenal Medullary autografts into the basal ganglia of Cebuc monkeys: injury-induced regeneration. Exp Neurol 102: 76-91, 1988.
54. Fine A, Hunt SP, Oertel WH, Nomoto M, Chong PN, Bond A, Waters C, Temlett JA, Annett L, and Dunnett S. Transplantation of embryonic marmoset dopaminergic neurons to the corpus striatum of marmosets rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Prog Brain Res 78: 479-489, 1988.
55. Fink JS, Schumacher JM, Ellias SL, Paler EP, Saint-Hilaire M, Shannon K, Penn R, Starr P, VanHorne C, Knott HS, Dempsey PK, Fischman AJ, Raineri R, Manhart C, Dinsmore J, and Isacson O. Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results. Cell Transp 9: 273-278, 2000.
56. Flores J, Cepeda IL, Cornfeldt ML, O'Kusky JR, and Doudet DJ. Characterization and survival of long-term implants of human retinal pigment epithelial cells attached to gelatin microcarriers in a model of Parkinson's disease. J Neuropathol Exp Neurol 66: 585-596, 2007.
57. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, and Fahn S. Transplantation of embryonic dopamine neurons for treatment of severe Parkinson's disease. NEJM 344: 710-719, 2001.
58. Freed WJ, Morihisia JM, Spoor E, Hoffer BJ, Olson L, Seiger A, and Wyatt RJ. Transplanted adrenal chromaffin cells in rat brain reduce lesion-induced rotational behaviour. Nature 292: 351-352, 1981.
59. Galpern WR, Burns LH, Deacon TW, Dinsmore J, and Isacson O. Xenotransplantation of porcine fetal ventral mesencephalon in a rat model of Parkinson's disease: Functional recovery and graft morphology. Exp Neurol 140: 1-13, 1996.
60. Gash DM, Zhang Z, Ovadia A, Cass WA, Yi A, Simmerman L, Russell D, Martin D, Lapchak PA, Collins F, Hoffer BJ, and Gerhardt GA. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 380: 252-255, 1996.
61. Goetz CG, Olanow CW, Koller WC, Penn RD, Cahill D, Morantz R, Stebbins G, Tanner CM, Klawans HL, and Shannon KM. Multicenter study of autologus adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson's disease. NEJM 321: 324-327, 1989.
62. Gould E, Reeves AJ, Graziano MS, and Gross CG. Neurogenesis in the neocortex of adult primates. Science 286: 548-552, 1999.
63. Hagell P, Piccini P, Bjorklund A, Brundin P, Rehncrona S, Widner H, Crabb L, Pavese N, Oertel WH, Quinn N, Brooks DJ, and Lindvall O. Dyskinesias following neural transplantation in Parkinson's disease. Nat Neurosci 5: 627-628, 2002.
64. Hagell P and Widner H. Clinical rating of dyskinesias in Parkinson's disease: Use and reliability of a new rating scale. Mov Disord 14: 488-455, 1999.
65. Halme DG and Kessler DA. FDA regulation of stem-cell-based therapies. NEJM 355: 1730-1735, 2006.
66. Hao G, Yao Y, Wang J, Zhang L, Viroonchatapan N, and Wang ZZ. Intrastriatal grafting of glomus cells ameliorates behavioral defects of Parkinsonian rats. Physiol Behav 77: 519-525, 2002.
67. Hedlund E, Pruszak J, Lardaro T, Ludwig W, Vinuela A, Kin K-S, and 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 disease. Stem Cells 26: 1526-1536, 2008.
68. Hellman MA, Panet H, Barhum Y, Melamed E, and Offen D. Increased survival and migration of engrafted mesenchymal bone marrow stem cells in 6-hdroxydopamine-lesioned rodents. Neurosci Lett 395: 124-128, 2006.
69. Hitchcock ER, Clough C, Hughes R, and Kenny B. Embryos and Parkinson's disease. Lancet 1: 1274, 1988.
70. Hurlbut WB. Altered nuclear transfer: A way forward for embryonic stem cell research. Stem Cell Rev 1: 293-300, 2005.
71. Hwang WS, Roh SI, Lee BC, Kang SK, Kwon DK, Kim S, Kim SJ, Park SW, Kwon HS, Lee CK, Lee JB, Kim JM, Ahn C, Paek SH, Chang SS, Koo JJ, Yoon HS, Hwang JH, Hwang YY, Park YS Oh SK, Kim HS, Park JH, Moon SY, and Schatten G. Patient-specific embryonic stem cells derived from human SCNT blastocysts. Science 308: 1777-1783, 2005.
72. Iacovitti L, Donaldson AE, Marshall CE, Suon S, and Yang M. Protocol for the differentiation of human embryonic stem cells into dopaminergic neurons using only chemically defined human additives: studies in vitro and in vivo. Brain Res 1127: 19-25, 2007.
73. Iacovitti L, Stull ND, and Johnston K. Melatonin rescues dopamine neurons from cell death in tissue culture models of oxidative stress. Brain Res 768: 317-326, 1997.
74. Iacovitti L, Stull ND, and Mishizen A. Neurotransmitters, KCl and antioxidants rescue striatal neurons from apoptotic cell death in culture. Brain Res 816: 276-285, 1999.
75. Isacson O, Costantini L, Schumacher JM, Cicchetti F, Chung S, and Kim K. Cell implantation therapies for Parkinson's disease using neural stem, transgenic or xenogeneic donor cells. Parkinsonism Relat Disord 7: 205-212, 2001.
76. Itakura T, Uematsu Y, Nakao N, Nakai E, and Nakai K. Transplantation of autologous sympathetic ganglion into the brain with Parkinson's disease: Long-term follow-up of 35 cases. Stereotact Funct Neurosurg 69: 112-115, 1997.
77. Jacques DB, Kopyov OV, Eagle KS, Carter T, and Lieberman A. Outcomes and complications of fetal tissue transplantation in Parkinson's disease. Stereotact Funct Neurosurg 72: 219-224, 1999.
78. Kachergus J, Mata IF, Hulihan M, Taylor JP, Lincoln S, Aasly J, Gibson JM, Ross OA, Lynch T, Wiley J, Payami H, Nutt J, Maraganore DM, Czyzewski K, Styczynska M, Wszolek ZK, Farrer MJ, and Toft M. Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: Evidence of a common founder across European populations. Am J Hum Genet 76: 672-680, 2005.
79. Kaplan MS and Hinds JW. Neurogenesis in the adult rat: Electron microscopic analysis of light radioautographs. Science 197: 1092-1094, 1977.
80. Kastenberg ZJ and Odorico JS. Alternative sources of pluripotency: science, ethics, and stem cells. Transplant Rev 22: 215-222, 2008.
81. Kempermann G, Kuhn HG and Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature 386: 493-495, 1997.
82. Kim SU, Park IH, Kim TH, Kim KS, Choi HB, Hong SH, Bang JH, Lee MA, Joo IS, Lee CS, and Kim YS. Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson's disease. Neuropathology 26: 129-140, 2006.
83. Kishima H, Poyot T, Bloch J, Dauguet J, Conde F, Dolle F, Hinen F, Pralong W, Palfi S, Deglon N, Aebischer P, and Hantraye P. Encapsulated GDN-producing C2C12 cells for Parkinson's disease: A pre-clinical study in chronic MPTP-treated baboons. Neuroiol Dis 16: 428-439, 2004.
84. Kopyov O, Jacques DS, Lieberman A, Duma CM, and Rogers RL. Outcome following intrastriatal fetal mesencephalic grafts for Parkinson's patients is directly related to the volume of grafted tissue. Exp Neurol 146: 536-545, 1997.
85. Kordower JH, Chu Y, Hauser RA, Freeman TB, and Olanow CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nature Med 14: 504-506, 2008.
86. Kordower J, Freeman T, Snow B, Vingerhoets F, Mufson E, Sanberg P, Hjauser RA, Smith DA, Nauert GM, Perl DP, et al. Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson's disease. N Engl J Med 332: 1118-1124, 1995.
87. Kordower JH, Styren S, Clarke M, DeKosky ST, Olanow CW, and Freeman TB. Fetal grafting for Parkinson's disease: Expression of immune markers in two patients with functional fetal nigral implants. Cell Transplant 6(3): 213-9, 1997.
88. Langston JW. The Parkinson's complex: Parkinsonism is just the tip of the iceberg. Annals Neurol 59: 591-596, 2006.
89. Langston JW, Ballard P, Tetrud JW, and Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979-980, 1983.
90. Langston JW, Langston EB, and Irwin I. MPTP-induced parkinsonism in human and non-human primates: Clinical and experimental aspects. Acta Neurol Scand Suppl 100: 49-54, 1984.
91. Langston JW, Quik M, Petzinger G, Jakowec M, and Di Monte DA. Investigating levodopa-induced dyskinesias in the parkinsonsian primate. Ann Neurol 47: S79-89, 2000.
92. Lee SH, Lumelsky N, Studer L, Auerbach JM, and McKay RD. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 18: 675-679, 2000.
93. Leranth C, Roth RH, Elsworth JD, Naftolin F, Horvath TL, and Redmond DE Jr. Estrogen is essential for maintaining nigrostriatal dopamine neurons in primates: Implications for Parkinson's disease and memory. J Neuroscience 20: 8604-8609, 2000.
94. Leranth C, Sladek J Jr, Roth R, and Redmond D Jr. Efferent synaptic connections of dopaminergic neurons grafted into the caudate nucleus of experimental induced parkinsonian monkeys are different than those of control animals. Exp Brain Res 123: 323-333, 1998.
95. Levy YS, Bahat-Stroomza M, Barzilay R, Burshtein A, Bulvik S, Barhum Y, Panet H, Melamed E, and Offen D. Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson's disease. Cytotherapy 10: 340-352, 2008.
96. Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, Lashley T, Quinn NP, Rehncrona S, Bjorklund A, Widner H, Revesz T, Lindvall O, and Brundin P. Lewy bodeies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med 14: 501-503, 2008.
97. Lin LF, Doherty DH, Lile JD, Bektesh S, and Collins F. GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260: 1130-1132, 1993.
98. Lindvall O, Brundin P, Widner H, Rehncrona S, Gustavii B, Frackowiak R, Leenders KL, Sawle G, Rothwell JC, Marsden CD, et al. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. Science 247: 574-577, 1990.
99. Lindvall O, Rehncrona S, Brundin P, Gustavii B, Astedt B, Widner H, Lindholm T, Bjorklund A, Leenders KL, Rothwell JC, 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 46(6): 615-31, 1989.
100. Liu H, Zhu F, Yong J, Zhang P, Hou P, Li H, Jiang W, Cai J, Liu M, Cui K, Qu X, Xiang T, Lu D, Gao G, Ji W, Ding M, and Deng H. Generation of induced pluripotent stem cells from adult rhesus monkey fibroblasts. Cell Stem Cell 3: 587-590, 2008.
101. Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, and Brice A; French Parkinson's Disease Genetics Study Group; European Consortium on Genetic Susceptibility in Parkinson's Disease. Association between earlyonset Parkinson's disease and mutations in the parkin gene. N Engl J Med 342: 1560-1567, 2000.
102. Ludwig TE, Bergendahl V, Levenstein MS, Yu J, Probasco MD, and Thomson JA. Feeder-independent culture of human embryonic stem cells. Nat Methods 3: 637-646, 2006.
103. Lundblad M, Picconi B, Lindgren H, and Cenci MA. A model of L-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: Relation to motor and cellular parameters of nigrostriatal function. Neurobiol Dis 16: 110-123, 2004.
104. Luquin MR, Montoro RJ, Guillen J, Saldise L, Insausti R, Del Rio J, and Lopez-Barneo J. Recovery of chronic parkinsonian monkeys by autotransplants of carotid body cell aggregates into putamen. Neuron 22: 743-750, 1999.
105. Madrazo I, Drucker-Colin R, Diaz V, Martinez-Mata J, Torres C, and Becerril JJ. Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson's disease. N Engl J Med 316: 831-834, 1987.
106. Marras C, McDermott MP, Rochon PA, Tanner CM, Naglie G, and Lang AE, Parkinson Study Group DATATOP Investigators. Predictors of deterioration in health-related quality of life in Parkinson's disease: Results from the DATATOP trial. Mov Disord 23: 653-659, 2008.
107. McCoy MK, Martinez TN, Ruhn KA, Wrage PC, Keefer EW, Botterman BR, and Tansey KE. Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease. Exp Neurol 210: 14-29, 2008.
108. Mendez I, Vinuela A, Astradsson A, Mukhida K, Hallett P, Robertson H, Tierney T, Holness R, Dagher A, Trojanowski J, and Isacson O. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nature Med 14: 507-509, 2008.
109. Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, and Crain B. Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci USA 100: 1364-1369, 2003.
110. Minguez-Castellanos A, Escamilla-Sevilla F, Hotton GR, Toledo-Aral JJ, Ortega-Moreno A, Mendez-Ferrer S, Martin-Linares JM, Katati MJ, Mir P, Villadiego J, Meersmans M, Perez-Garcia M, Brooks DJ, Arjona V, and Lopez-Barneo J. Carotid body autotransplantation in Parkinson's disease: A clinical and positron emission tomography study. J Neurol Neurosurg Psychiatry 78: 825-831, 2007.
111. Morihisa JM, Nakamura RK, Freed WJ, Mishkin M, and Wyatt RJ. Adrenal medulla grafts survive and exhibit catecholamine-specific fluorescence in the primate brain. Exp Neurol 84: 643-653, 1984.
112. Mundy A and Winslow R. (2009, January 23). First Embryonic Stem-Cell Trial Gets Approval from the FDA. Wall Street Journal, p A12.
113. Nakao N, Itakura T, Uematsu Y, and Komai N. Transplantation of cultured sympathetic ganglionic neurons into parkinsonian rat brain: Survival and function of graft. Acta Neurochir 133: 61-67, 1995.
114. Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, Shannon KM, Nauert GM, Perl DP, Godbold J, and Freeman TB. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease. Ann Neurol 54: 403-414, 2003.
115. Paquette JA, Kumpf SW, Streck RD, Thomson JJ, Chapin RE, and Stedman DB. Assessment of the Embryonic Stem Cell Test and application and use in the pharmaceutical industry. Birth Defects Res B Dev Reprod Toxicol 83: 104-111, 2008.
116. Perrier AL, Tabar V, Barberi T, Rubio ME, Bruses J, Topf N, Harrison NL, and Studer L. Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci USA101: 12543-12548, 2004.
117. Plunkett RJ, Bankiewicz KS, Cummins AC, Miletich RS, Schwartz JP, and Oldfield EH. Long-term evaluation of hemiparkinsonian monkeys after adrenal autografting or cavitation alone. J Neurosurg 73: 918-926, 1990.
118. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, and Nussbaum RL. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 276: 2045-2047, 1997.
119. Przedborski S and Vila M. The 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine mouse model. Ann NYAS 991: 189-198, 2003.
120. Rakic P. Immigration denied. Nature 427: 685-686, 2004.
121. Redmond ED Jr. Cellular replacement therapy for Parkinson's disease-Where are we today? The Neuroscientist 8: 457-488, 2002.
122. Redmond DE, Bjugstad KB, Teng YD, 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, and Snyder EY. Behavioral improvement in a primate model is associated with multiple homeostatic effects of human neural stem cells. Proc Natl Acad Sci USA 104: 12175-12180, 2007.
123. Redmond DE Jr, Naftolin F, Collier TJ, Leranth C, Robbins RJ, Cladek CD, Roth RH, and Sladek JR Jr. Cryopreservation, culture, and transplantation of human fetal mesencephalic tissue into monkeys. Science 242: 768-771, 1988.
124. Redmond DE Jr, Ourednik J, Ourdenik V, Roth RH, Elsworth JD, Sladek JR Jr, Teng YD, Hack M, Sidman RL, and Snyder EY. Human neural stem cells survive, migrate, and differentiate into TH-positive neurons in mesencephalon of adult MPTP-treated non-human primates. Exp Neurol 164: 445, 2000.
125. Redmond DE Jr, Sladek JR Jr, Roth RH, Collier TJ, Elsworth JD, Deutch AY, and Haber S. Fetal neuronal grafts in monkeys given methylphenyltetrahydropyridine. Lancet 1: 1125-1127, 1986.
126. Redmond DE Jr, Vinuela A, Kordower JH, and Isacson O. Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson's disease. Neurolbiol Dis 29: 103-116, 2008.
127. Ridley RM, Baker HF, Annett LE, Dunnett SB, Torres EM, and Fine A. Behavioral assessment of the ability of intracerebral embryonic neural tissue grafts to ameliorate the effects of brain damage in marmosets. Mol Neurobiol 9: 207-223, 1994.
128. Roitberg BZ, Mangubat E, Chen EY, Sugaya K, Thulborn KR, Kordower JH, Pawer A, Konecny T, and Emborg ME. Survival and early differentiation of human neural stem cells transplanted in a non-human primate model of stroke. J Neurosurg 105: 96-102, 2006.
129. Roitberg B, Urbaniak K, and Emborg M. Cell transplantation for Parkinson's disease. Neurol Res 26: 355-362, 2004.
130. Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM Gupta N, Kunwar S, Lawton MT, McDermott MW, Parsa AT, Manuel-Garcia Verdugo J, Berger MS, Alvarez-Buylla A. Unique astrocyte ribbon I adult human brain contains neural stem cells but lacks chain migration. Nature 427: 740-744, 2004.
131. Sanberg PR, Willing AE, Garbuzova-Davis S, Saporta S, Liu G, Davis Sanberg C, Bickford PC, Klasko SK, and Elbadri NS. Umbilical cord blood-derived stem cells and brain repair. Ann NY Acad Sci 1049: 67-83, 2005.
132. Sanchez-Pernaute R, Lee H, Patterson M, Reske-Nielsen C, Yoshizaki T, Sonntag KC, Studer L, and Isacson O. Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease. Brain 131: 2127-2139, 2008.
133. Sanchez-Pernaute R, Studer L, Bankiewicz KS, Major EO, and McKay RD. In vitro generation and transplantation of precursor-derived human dopamine neurons. J Neurosci Res 65: 284-288, 2001.
134. Sanchez-Pernaute R, Studer L, Ferrari D, Perrier A, Lee H, Vinuela A, and Isacson O. Long-term survival of dopaminergic neurons derived from parthenogenetic primate embryonic stem cells (cyno-1) after transplantation. Stem Cells 23: 914-922, 2005.
135. Schueler SB, Ortega JD, Sagen J, and Kordower JH. Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: A novel hypothesis of adrenal graft viability. J Neurosci 13: 4496-4510, 1993.
136. Schulz TC, Noggle SA, Palmarini GM, Weiler DA, Lyons IG, Pensa KA, Meedeniya CB, Davidson BP, Lambert NA, and Condie BG. Differentiation of human embryonic stem cells to dopaminergic neurons in serum-free suspension culture. Stem Cells 22: 1218-1238, 2004.
137. Sherer TB, Fiske BK, Svendson CN, Lang AE, and Langston JW. Crossroads in GDNF therapy for Parkinson's disease. Mov Disord 21: 136-141, 2006.
138. Shintani A, Nakao N, Kakishita K, and Itakura T. Generation of dopamine neurons from embryonic stem cells in the presence of the neuralizing activity of bone marrow stromal cells derived from adult mice. J Neurosci Res 86: 2829-2838, 2008.
139. Sladek JR Jr, Bjugstad KB, Collier TJ, Bundock EA, Blanchard BC, Elsworth JD, Roth RH, and Redmond DE Jr. Embryonic substantia nigra grafts show directional outgrowth to cografted striatal grafts and potential for pathway reconstruction in non-human primate. Cell Transplant 17: 427-444, 2008.
140. Sladek JR Jr, Collier TJ, Elsworth JD, Roth RH, Taylor JR, and Redmond DE Jr. Intrastriatal grafts from multiple donors do not result in a proportional increase of survival of dopamine neurons in non-human primates. Cell Transplant 7: 87-96, 1998.
141. Sladek JR Jr, Collier TJ, Haber SN, Roth RH, and Redmond DE Jr. Survival and growth of fetal catecholamine neurons transplanted into primate brain. Brain Res Bull 17: 809-818, 1986.
142. Sladek JR Jr, Elsworth JD, Roth RH, Evans LE, Collier TJ, Cooper SJ, Taylor JR, and Redmond DE Jr. Fetal dopamine cell survival after transplantation is dramatically improved at a critical donor gestation age in non-human primates. Exp Neurol 122: 16-27, 1993.
143. Snyder EY and Macklis JD. Multipotent neural progenitor or stem-like cells may be uniquely suited for therapy for some neurodegenerative conditions. Clin Neurosci 3: 310-316, 1995.
144. Soderstrom KE, Meredith G, Freeman TB, McGuire SO, Collier TJ, Wu Q, and Steece-Collier K. The synaptic impact of the host immune response in a parkinsonian allograft rat model: Influence on graft-derived aberrant behaviors. Neurobiol Dis 32: 229-242, 2008.
145. Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, and Jaenisch R. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 136: 964-977, 2009.
146. Sonntag K-C, Pruszak J. Yoshizaki T, van Arensbergen J, Sanchez-Pernaute R, and Isacson O. Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist Noggin. Stem Cells 25: 411-418, 2007.
147. Spillantini MG. Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are alpha-synucleinopathies. Parkinsonism Relat Disord 5: 157-162, 1999.
148. Suhr ST and Gage FH. Gene therapy for neurologic disease. Arch Neurol 50: 1252-1268, 1993.
149. Svendsen CN. Neural stem cells for brain repair. Alzheimer's Res 3: 131-135, 1997.
150. Svendsen CN and Smith AG. New prospects for human stem-cell therapy in the nervous system. Trends Neurosci 22: 357-364, 1999.
151. Swanson CR, Sesso SL, and Emborg ME. Can we prevent Parkinson's disease? Front Biosci 14: 1642-1660, 2009.
152. Tabar V, Tomishima M, Panagiotakos G, Wakayama S, Menon J, Chan B, Mizutani E, Al-Shamy G, Ohta H, Wakayama T, and Studer L. Therapeutic cloning in individual parkinsonian mice. Nat Med 14: 379-381, 2008.
153. Tai Y and Svendsen CN. Stem cells as a potential treatment of neurological disorders. Curr Opin Pharm 4: 98-104, 2004.
154. 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, and Hashimoto N. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson's primate model. J Clin Invest 115: 102-109, 2005.
155. Takahashi K, Okita K, Nakagawa M, and Yamanaka S. Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc 2: 3081-3089, 2007.
156. Tambur AR. Transplantation immunology and the central nervous system. Neurol Res 26: 243-255, 2004.
157. Tang B, Xiong H, Sun P, Zhang Y, Wang D, Hu Z, Zhu Z, Ma H, Pan Q, Xia JH, Xia K, and Zhang Z. Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease. Hum Mol Genet 15: 1816-1825, 2006.
158. Taylor JR, Elsworth JD, Roth RH, Collier TJ, and Sladek JR Jr, Redmond DE Jr. Improvements in MPTP-induced object retrieval deficits and behavioral deficits after fetal nigral grafting in monkeys. Prog Brain Res 82: 543-559, 1990.
159. Taylor JR, Elsworth JD, Roth RH, Sladek JR Jr, Collier TJ, and Redmond DE Jr. Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: A comparison with other types of grafts as controls. Exp Brain Res 85: 335-348, 1991.
160. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, and Jones JM. Embryonic stem cell lines derived from human blastocysts. Science 282: 1145-1147, 1998.
161. Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Becker RA, and Hearn JP. Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci USA 92: 7844-7848, 1995.
162. Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, and Hearn JP. Pluripotet cell lines derived from common marmoset (Callithrix jacchus) blastocytes. Biol Reprod 55: 254-259, 1996.
163. Thomson JA and Marshall VS. Primate embryonic stem cells. Curr Top Dev Biol 38: 133-165, 1998.
164. Thomson JA, Marshall VS, and Trojanowski JQ. Neural differentiation of rhesus embryonic stem cells. APMIS 106: 149-156, 1998.
165. Toledo-Aral JJ, Mendez-Ferrer S, Pardal R, Echevarria M, and Lopez-Barneo J. Trophic restoration of the nigrostriatal dopaminergic pathway in long-term carotid body grafted parkinsonian rats. J Neurosci 23: 141-148, 2003.
166. Tretiakoff C. Contribution a l'étude de l'anatomic pathologique du locus niger de soemmering avec quelques déductions relatives à la pathologie des troubles du tonus musculaire et de la maladie de Parkinson. These pour le doctorat en medicine. Paris: These de Paris, 1-24, 1919.
167. Uchida N, Buck DW, He D, Reitsma MJ, Masek M, Phan TV, Tsukamoto AS, Gage FH, and Weissman IL. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci USA 97: 14720-14725, 2000.
168. Videnovic A and Metman LV. Deep brain stimulation for Parkinson's disease: Prevalence of adverse events and need for standardized reporting. Mov Disord 23: 343-349, 2008.
169. Villadiego J, Mendez-Ferrer S, Valdes-Sanches T, Silos-Santiago I, Farinas I, Lopez-Barneo J, and Toledo-Aral JJ. Selective glial cell line-derived neurotrophic factor production in adult dopaminergic carotid body cells in situ and after intrastriatal transplantation. J Neurosci 25: 4091-4098, 2005.
170. Vogel G. Parkinson's research fetal cell transplant draws fire. Science 291: 260-261, 2001.
171. Watts RL, Raiser CD, Stover NP, Cornfeldt ML, Schweikert AW, Allen RC, Subramian T, Doudet D, Honey CR, and Bakay RA. Stereotaxic intrastriatal implantation of human retinal pigment epithelial (hRPE) cells attached to gelatin microcarriers: A potential new cell therapy for Parkinson's disease. J Neural Transm Suppl 65: 215-227, 2003.
172. Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, and Jaenisch R. 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 15: 5856-58561, 2008.
173. Widner H. NIH neural transplantation funding [letter]. Science 263: 737, 1994.
174. Williams N. Setback spurs Parkinson's disease research. Curr Biol 11: R285-286, 2001.
175. Yan Y, Yang D, Zarnowska ED, Du Z, Werbel B, Valliere C, Pearce RA, Thomson JA, and Zhang SC. Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23: 781-790, 2005.
176. Yang D, Zhang Z-J, Oldenburg M, Ayala M, and Zhang S-C. Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats. Stem Cells 26: 55-63, 2008.
177. Yin D, Valles FE, Fiandaca MS, Forsayeth J, Larson P, Starr P, and Bankiewicz KS. Striatal volume differences between non-human and human primates. J Neurosci Methods 176: 200-205, 2009.
178. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, and Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science 318: 1917-1920, 2007.
179. Yurek DM, Steece-Collier K, Collier TJ, and Sladek JR Jr. Chronic levodopa impairs the recovery of dopamine agonist-induced rotational behavior following neural grafting. Exp Brain Res 86: 97-107, 1991.
180. Zhan X, Hill C, Brayton CF, and Shamblott MJ. Cells derived from human umbilical cord blood support the long-term growth of undifferentiated human embryonic stem cells. Cloning Stem Cells 10: 513-522, 2008.
181. Zhang HL, Wu JJ, Ren HM, Wang J, Su YR, and Jiang YP. Therapeutic effect of microencapsulated porcine retinal pigmented epithelial cell transplantation on rat model of Parkinson's disease. Neurosci Bull 23: 137-144, 2007.
182. Zhang SC, Wernig M, Duncan ID, Brustle O, and Thomson JA. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol 19: 1129-1133, 2001.
183. Zeng X, Cai J, Chen J, Luo Y, You Z-B, Fotter E, Wang Y, Harvey B, Miura T, Backman C, Chen G-J, Rao MS, and Freed WJ. Dopaminergic differentiation of human embryonic stem cells. Stem Cells 22: 925-940, 2004.