Cell replacement therapy for Parkinson’s disease: how close are we to the clinic?

References

• Poewe W. The natural history of Parkinson’s disease. J. Neurol.253(S7), vii2–vii6 (2006).
   PubMedGoogle Scholar
• Arenas E. Towards stem cell replacement therapies for Parkinson’s disease. Biochem. Biophys. Res. Commun.396(1), 152–156 (2010).
   PubMed Web of Science ®Google Scholar
• Arias-Carrión O, Yuan TF. Autologous neural stem cell transplantation: a new treatment option for Parkinson’s disease? Med. Hypotheses73(5), 757–759 (2009).
   Google Scholar
• Fahn S, Oakes D, Shoulson I et al. Levodopa and the progression of Parkinson’s disease. N. Engl. J. Med.351(24), 2498–2508 (2004).
   PubMed Web of Science ®Google Scholar
• Lindvall O, Kokaia Z. Stem cells in human neurodegenerative disorders – time for clinical translation? J. Clin. Invest.120(1), 29–40 (2010).
   PubMed Web of Science ®Google Scholar
• Yokochi M. Reevaluation of levodopa therapy for the treatment of advanced Parkinson’s disease. Parkinsonism Relat. Disord.15(Suppl. 1), S25–S30 (2009).
   Google Scholar
• Olson L, Seiger A. Brain tissue transplanted to the anterior chamber of the eye. 1. Fluorescence histochemistry of immature catecholamine and 5-hydroxytryptamine neurons reinnervating the rat iris. Z. Zellforsch. Mikrosk. Anat.135(2), 175–194 (1972).
   Google Scholar
• Seiger A, Olson L, Farnebo LO. Brain tissue transplanted to the anterior chamber of the eye. 4. Drug-modulated transmitter release in central monoamine nerve terminals lacking normal postsynaptic receptors. Cell Tissue Res.165(2), 157–170 (1976).
   Google Scholar
• Hoffer B, Olson L, Seiger A, Bloom F. Formation of a functional adrenergic input to intraocular cerebellar grafts: ingrowth of inhibitory sympathetic fibers. J. Neurobiol.6(6), 565–585 (1975).
   Google Scholar
• Freed WJ, Perlow MJ, Karoum F et al. Restoration of dopaminergic function by grafting of fetal rat substantia nigra to the caudate nucleus: long-term behavioral, biochemical, and histochemical studies. Ann. Neurol.8(5), 510–519 (1980).
   PubMed Web of Science ®Google Scholar
• Björklund A, Stenevi U, Svendgaard N. Growth of transplanted monoaminergic neurones into the adult hippocampus along the perforant path. Nature262(5571), 787–790 (1976).
   Google Scholar
• Stenevi U, Björklund A. Transplantation techniques for the study of regeneration in the central nervous system. Prog. Brain Res.48, 101–112 (1978).
   Google Scholar
• Stenevi U, Björklund A, Svendgaard NA. Transplantation of central and peripheral monoamine neurons to the adult rat brain: techniques and conditions for survival. Brain Res.114(1), 1–20 (1976).
   PubMed Web of Science ®Google Scholar
• Wakeman DR, Dodiya HB, Kordower JH. Cell transplantation and gene therapy in Parkinson’s disease. Mt Sinai J. Med.78(1), 126–158 (2011).
   Google Scholar
• Dunnett SB, Björklund A, Schmidt RH, Stenevi U, Iversen SD. Intracerebral grafting of neuronal cell suspensions. V. Behavioural recovery in rats with bilateral 6-OHDA lesions following implantation of nigral cell suspensions. Acta Physiol. Scand. Suppl.522, 39–47 (1983).
   PubMedGoogle Scholar
• Dunnett SB, Björklund A, Schmidt RH, Stenevi U, Iversen SD. Intracerebral grafting of neuronal cell suspensions. IV. Behavioural recovery in rats with unilateral 6-OHDA lesions following implantation of nigral cell suspensions in different forebrain sites. Acta Physiol. Scand. Suppl.522, 29–37 (1983).
   Google Scholar
• Björklund A, Stenevi U, Schmidt RH, Dunnett SB, Gage FH. Intracerebral grafting of neuronal cell suspensions. I. Introduction and general methods of preparation. Acta Physiol. Scand. Suppl.522, 1–7 (1983).
   PubMedGoogle Scholar
• Björklund A, Stenevi U, Schmidt RH, Dunnett SB, Gage FH. Intracerebral grafting of neuronal cell suspensions. II. Survival and growth of nigral cell suspensions implanted in different brain sites. Acta Physiol. Scand. Suppl.522, 9–18 (1983).
   Google Scholar
• Brundin P, Isacson O, Gage FH, Björklund A. Intrastriatal grafting of dopamine-containing neuronal cell suspensions: effects of mixing with target or non-target cells. Brain Res.389(1–2), 77–84 (1986).
   Google Scholar
• Brundin P, Nilsson OG, Strecker RE et al. Behavioural effects of human fetal dopamine neurons grafted in a rat model of Parkinson’s disease. Exp. Brain Res.65(1), 235–240 (1986).
   PubMed Web of Science ®Google Scholar
• Brundin P, Björklund A. Survival, growth and function of dopaminergic neurons grafted to the brain. Prog. Brain Res.71, 293–308 (1987).
   PubMedGoogle Scholar
• Freed WJ, Morihisa JM, Spoor E et al. Transplanted adrenal chromaffin cells in rat brain reduce lesion-induced rotational behaviour. Nature292(5821), 351–352 (1981).
   PubMedGoogle Scholar
• Backlund EO, Granberg PO, Hamberger B et al. Transplantation of adrenal medullary tissue to striatum in parkinsonism. First clinical trials. J. Neurosurg.62(2), 169–173 (1985).
   PubMed Web of Science ®Google Scholar
• Madrazo I, Drucker-Colín R, Díaz V et al. Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson’s disease. N. Engl. J. Med.316(14), 831–834 (1987).
   PubMed Web of Science ®Google Scholar
• Morihisa JM, Nakamura RK, Freed WJ, Mishkin M, Wyatt RJ. Adrenal medulla grafts survive and exhibit catecholamine-specific fluorescence in the primate brain. Exp. Neurol.84(3), 643–653 (1984).
   Google Scholar
• Plunkett RJ, Bankiewicz KS, Cummins AC et al. Long-term evaluation of hemiparkinsonian monkeys after adrenal autografting or cavitation alone. J. Neurosurg.73(6), 918–926 (1990).
   Google Scholar
• Goetz CG, Olanow CW, Koller WC et al. Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson’s disease. N. Engl. J. Med.320(6), 337–341 (1989).
   PubMed Web of Science ®Google Scholar
• Vidaltamayo R, Bargas J, Covarrubias L et al. Stem cell therapy for Parkinson’s disease: a road map for a successful future. Stem Cells Dev.19(3), 311–320 (2010).
   Google Scholar
• Freed CR, Greene PE, Breeze RE et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N. Engl. J. Med.344(10), 710–719 (2001).
   PubMed Web of Science ®Google Scholar
• Bjorklund LM, Sánchez-Pernaute R, Chung S et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc. Natl Acad. Sci. USA99(4), 2344–2349 (2002).
   PubMed Web of Science ®Google Scholar
• O’Keeffe FE, Scott SA, Tyers P et al. Induction of A9 dopaminergic neurons from neural stem cells improves motor function in an animal model of Parkinson’s disease. Brain131(Pt 3), 630–641 (2008).
   PubMed Web of Science ®Google Scholar
• Wernig M, Zhao J-P, Pruszak J et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson’s disease. Proc. Natl Acad. Sci. USA105(15), 5856–5861 (2008).
   PubMed Web of Science ®Google Scholar
• Dezawa M, Kanno H, Hoshino M et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J. Clin. Invest.113(12), 1701–1710 (2004).
   PubMed Web of Science ®Google Scholar
• Park HJ, Lee PH, Bang OY, Lee G, Ahn YH. Mesenchymal stem cells therapy exerts neuroprotection in a progressive animal model of Parkinson’s disease. J. Neurochem.107(1), 141–151 (2008).
   PubMed Web of Science ®Google Scholar
• Murrell W, Wetzig A, Donnellan M et al. Olfactory mucosa is a potential source for autologous stem cell therapy for Parkinson’s disease. Stem Cells26(8), 2183–2192 (2008).
   PubMed Web of Science ®Google Scholar
• Yasuhara T, Matsukawa N, Hara K et al. Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson’s disease. J. Neurosci.26(48), 12497–12511 (2006).
   PubMed Web of Science ®Google Scholar
• Kim J-H, Auerbach JM, Rodríguez-Gómez JA et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature418(6893), 50–56 (2002).
   PubMed Web of Science ®Google Scholar
• Cai J, Yang M, Poremsky E et al. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats. Stem Cells Dev.19(7), 1017–1023 (2010).
   PubMed Web of Science ®Google Scholar
• Levy YS, Bahat-Stroomza M, Barzilay R et al. Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson’s disease. Cytotherapy10(4), 340–352 (2008).
   PubMed Web of Science ®Google Scholar
• Lindvall O, Kokaia Z. Prospects of stem cell therapy for replacing dopamine neurons in Parkinson’s disease. Trends Pharmacol. Sci.30(5), 260–267 (2009).
   PubMed Web of Science ®Google Scholar
• Galpern WR, Burns LH, Deacon TW, Dinsmore J, 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), 1–13 (1996).
   PubMed Web of Science ®Google Scholar
• Fink JS, Schumacher JM, Ellias SL et al. Porcine xenografts in Parkinson’s disease and Huntington’s disease patients: preliminary results. Cell Transplant.9(2), 273–278 (2000).
   PubMed Web of Science ®Google Scholar
• Fitzpatrick KM, Raschke J, Emborg ME. Cell-based therapies for Parkinson’s disease: past, present, and future. Antioxid. Redox Signal.11(9), 2189–2208 (2009).
   Google Scholar
• Roitberg B, Urbaniak K, Emborg M. Cell transplantation for Parkinson’s disease. Neurol. Res.26(4), 355–362 (2004).
   PubMed Web of Science ®Google Scholar
• Bakay RAE, Raiser CD, Stover NP et al. Implantation of Spheramine in advanced Parkinson’s disease (PD). Front. Biosci.9, 592–602 (2004).
   PubMed Web of Science ®Google Scholar
• Doudet DJ, Cornfeldt ML, Honey CR, Schweikert AW, Allen RC. PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson’s disease. Exp. Neurol.189(2), 361–368 (2004).
   PubMed Web of Science ®Google Scholar
• Stover NP, Bakay RAE, Subramanian T et al. Intrastriatal implantation of human retinal pigment epithelial cells attached to microcarriers in advanced Parkinson disease. Arch. Neurol.62(12), 1833–1837 (2005).
   PubMed Web of Science ®Google Scholar
• Madrazo I, León V, Torres C et al. Transplantation of fetal substantia nigra and adrenal medulla to the caudate nucleus in two patients with Parkinson’s disease. N. Engl. J. Med.318(1), 51 (1988).
   PubMed Web of Science ®Google Scholar
• Nakao N, Itakura T, Uematsu Y, Komai N. Transplantation of cultured sympathetic ganglionic neurons into parkinsonian rat brain: survival and function of graft. Acta Neurochir. (Wien.)133(1–2), 61–67 (1995).
   Google Scholar
• Itakura T, Uematsu Y, Nakao N, Nakai E, 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(1–4 Pt 2), 112–115 (1997).
   Google Scholar
• Gonzalez C, Almaraz L, Obeso A, Rigual R. Carotid body chemoreceptors: from natural stimuli to sensory discharges. Physiol. Rev.74(4), 829–898 (1994).
   PubMed Web of Science ®Google Scholar
• Hao G, Yao Y, Wang J et al. Intrastriatal grafting of glomus cells ameliorates behavioral defects of Parkinsonian rats. Physiol. Behav.77(4–5), 519–525 (2002).
   PubMed Web of Science ®Google Scholar
• Luquin MR, Montoro RJ, Guillén J et al. Recovery of chronic parkinsonian monkeys by autotransplants of carotid body cell aggregates into putamen. Neuron22(4), 743–750 (1999).
   PubMed Web of Science ®Google Scholar
• Arjona V, Mínguez-Castellanos A, Montoro RJ et al. Autotransplantation of human carotid body cell aggregates for treatment of Parkinson’s disease. Neurosurgery53(2), 321–328; discussion 328–330 (2003).
   PubMed Web of Science ®Google Scholar
• Emsley JG, Mitchell BD, Kempermann G, Macklis JD. Adult neurogenesis and repair of the adult CNS with neural progenitors, precursors, and stem cells. Prog. Neurobiol.75(5), 321–341 (2005).
   PubMed Web of Science ®Google Scholar
• Gage FH, Ray J, Fisher LJ. Isolation, characterization, and use of stem cells from the CNS. Annu. Rev. Neurosci.18, 159–192 (1995).
   PubMed Web of Science ®Google Scholar
• Weiss S, Dunne C, Hewson J et al. Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci.16(23), 7599–7609 (1996).
   PubMed Web of Science ®Google Scholar
• McKay R. Stem cells in the central nervous system. Science276(5309), 66–71 (1997).
   PubMed Web of Science ®Google Scholar
• Gage FH. Mammalian neural stem cells. Science287(5457), 1433–1438 (2000).
   PubMed Web of Science ®Google Scholar
• Arsenijevic Y, Villemure JG, Brunet JF et al. Isolation of multipotent neural precursors residing in the cortex of the adult human brain. Exp. Neurol.170(1), 48–62 (2001).
   PubMed Web of Science ®Google Scholar
• Meyer AK, Maisel M, Hermann A, Stirl K, Storch A. Restorative approaches in Parkinson’s Disease: which cell type wins the race? J. Neurol. Sci.289(1–2), 93–103 (2010).
   PubMed Web of Science ®Google Scholar
• Svendsen CN, Caldwell MA, Shen J et al. Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson’s disease. Exp. Neurol.148(1), 135–146 (1997).
   PubMed Web of Science ®Google Scholar
• Parish CL, Castelo-Branco G, Rawal N et al. Wnt5a-treated midbrain neural stem cells improve dopamine cell replacement therapy in parkinsonian mice. J. Clin. Invest.118(1), 149–160 (2008).
   PubMedGoogle Scholar
• Studer L, Tabar V, McKay RD. Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nat. Neurosci.1(4), 290–295 (1998).
   PubMed Web of Science ®Google Scholar
• Jensen P, Pedersen EG, Zimmer J, Widmer HR, Meyer M. Functional effect of FGF2- and FGF8-expanded ventral mesencephalic precursor cells in a rat model of Parkinson’s disease. Brain Res.1218, 13–20 (2008).
   PubMedGoogle Scholar
• Papanikolaou T, Lennington JB, Betz A et al.In vitro generation of dopaminergic neurons from adult subventricular zone neural progenitor cells. Stem Cells Dev.17(1), 157–172 (2008).
   Google Scholar
• Shim J-W, Park C-H, Bae Y-C et al. Generation of functional dopamine neurons from neural precursor cells isolated from the subventricular zone and white matter of the adult rat brain using Nurr1 overexpression. Stem Cells25(5), 1252–1262 (2007).
   Google Scholar
• Kim HJ. Stem cell potential in Parkinson’s disease and molecular factors for the generation of dopamine neurons. Biochim. Biophys. Acta.1812(1), 1–11 (2011).
   Google Scholar
• Greco SJ, Rameshwar P. Recent advances and novel approaches in deriving neurons from stem cells. Mol. Biosyst.6(2), 324–328 (2010).
   Google Scholar
• Thomson JA, Itskovitz-Eldor J, Shapiro SS et al. Embryonic stem cell lines derived from human blastocysts. Science282(5391), 1145–1147 (1998).
   PubMed Web of Science ®Google Scholar
• Kawasaki H, Mizuseki K, Nishikawa S et al. Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron28(1), 31–40 (2000).
   PubMed Web of Science ®Google Scholar
• Roy NS, Cleren C, Singh SK et al. Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat. Med.12(11), 1259–1268 (2006).
   PubMed Web of Science ®Google Scholar
• Hwang DY, Kim DS, Kim DW. Human ES and iPS cells as cell sources for the treatment of Parkinson’s disease: current state and problems. J. Cell. Biochem.109(2), 292–301 (2010).
   Google Scholar
• Carpenter MK, Inokuma MS, Denham J et al. Enrichment of neurons and neural precursors from human embryonic stem cells. Exp. Neurol.172(2), 383–397 (2001).
   PubMed Web of Science ®Google Scholar
• Lee SH, Lumelsky N, Studer L, Auerbach JM, McKay RD. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat. Biotechnol.18(6), 675–679 (2000).
   PubMed Web of Science ®Google Scholar
• Perrier AL, Tabar V, Barberi T et al. Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc. Natl Acad. Sci. USA101(34), 12543–12548 (2004).
   PubMed Web of Science ®Google Scholar
• Cho MS, Hwang DY, Kim DW. Efficient derivation of functional dopaminergic neurons from human embryonic stem cells on a large scale. Nat. Protoc.3(12), 1888–1894 (2008).
   PubMed Web of Science ®Google Scholar
• Tondreau T, Lagneaux L, Dejeneffe M et al. Bone marrow-derived mesenchymal stem cells already express specific neural proteins before any differentiation. Differentiation72(7), 319–326 (2004).
   PubMed Web of Science ®Google Scholar
• Blondheim NR, Levy YS, Ben-Zur T et al. Human mesenchymal stem cells express neural genes, suggesting a neural predisposition. Stem Cells Dev.15(2), 141–164 (2006).
   PubMed Web of Science ®Google Scholar
• Deng J, Petersen BE, Steindler DA, Jorgensen ML, Laywell ED. Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells24(4), 1054–1064 (2006).
   PubMed Web of Science ®Google Scholar
• Minguell JJ, Fierro FA, Epuñan MJ, Erices AA, Sierralta WD. Nonstimulated human uncommitted mesenchymal stem cells express cell markers of mesenchymal and neural lineages. Stem Cells Dev.14(4), 408–414 (2005).
   PubMed Web of Science ®Google Scholar
• Li Y, Chen J, Wang L et al. Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neurosci. Lett.316(2), 67–70 (2001).
   PubMed Web of Science ®Google Scholar
• Tropel P, Platet N, Platel JC et al. Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells. Stem Cells24(12), 2868–2876 (2006).
   PubMedGoogle Scholar
• Wislet-Gendebien S, Hans G, Leprince P et al. Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells23(3), 392–402 (2005).
   PubMed Web of Science ®Google Scholar
• Cho KJ, Trzaska KA, Greco SJ et al. Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 α. Stem Cells.23(3), 383–391 (2005).
   PubMed Web of Science ®Google Scholar
• Barzilay R, Ben-Zur T, Bulvik S, Melamed E, Offen D. Lentiviral delivery of LMX1a enhances dopaminergic phenotype in differentiated human bone marrow mesenchymal stem cells. Stem Cells Dev.18(4), 591–601 (2009).
   PubMed Web of Science ®Google Scholar
• Trzaska KA, Kuzhikandathil EV, Rameshwar P. Specification of a dopaminergic phenotype from adult human mesenchymal stem cells. Stem Cells25(11), 2797–2808 (2007).
   PubMed Web of Science ®Google Scholar
• Trzaska KA, Reddy BY, Munoz JL et al. Loss of RE-1 silencing factor in mesenchymal stem cell-derived dopamine progenitors induces functional maturity. Mol. Cell. Neurosci.39(2), 285–290 (2008).
   PubMed Web of Science ®Google Scholar
• Trzaska KA, King CC, Li KY et al. Brain-derived neurotrophic factor facilitates maturation of mesenchymal stem cell-derived dopamine progenitors to functional neurons. J. Neurochem.110(3), 1058–1069 (2009).
   Google Scholar
• Barzilay R, Kan I, Ben-Zur T et al. Induction of human mesenchymal stem cells into dopamine-producing cells with different differentiation protocols. Stem Cells Dev.17(3), 547–554 (2008).
   PubMed Web of Science ®Google Scholar
• Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell126(4), 663–676 (2006).
   PubMed Web of Science ®Google Scholar
• Park I-H, Arora N, Huo H et al. Disease-specific induced pluripotent stem cells. Cell134(5), 877–886 (2008).
   PubMed Web of Science ®Google Scholar
• Soldner F, Hockemeyer D, Beard C et al. Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell136(5), 964–977 (2009).
   PubMed Web of Science ®Google Scholar
• Krizhanovsky V, Lowe SW. Stem cells: the promises and perils of p53. Nature460(7259), 1085–1086 (2009).
   PubMed Web of Science ®Google Scholar
• Kordower JH, Chu Y, Hauser RA, Freeman TB, Olanow CW. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat. Med.14(5), 504–506 (2008).
   PubMed Web of Science ®Google Scholar
• Vierbuchen T, Ostermeier A, Pang ZP et al. Direct conversion of fibroblasts to functional neurons by defined factors. Nature463(7284), 1035–1041 (2010).
   PubMed Web of Science ®Google Scholar
• Hynes M, Porter JA, Chiang C et al. Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron15(1), 35–44 (1995).
   PubMed Web of Science ®Google Scholar
• Wang MZ, Jin P, Bumcrot DA et al. Induction of dopaminergic neuron phenotype in the midbrain by Sonic hedgehog protein. Nat. Med.1(11), 1184–1188 (1995).
   PubMed Web of Science ®Google Scholar
• Ye W, Shimamura K, Rubenstein JL, Hynes MA, Rosenthal A. FGF and SHH signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell93(5), 755–766 (1998).
   PubMed Web of Science ®Google Scholar
• Moon RT, Brown JD, Torres M. WNTs modulate cell fate and behavior during vertebrate development. Trends Genet.13(4), 157–162 (1997).
   PubMed Web of Science ®Google Scholar
• Castelo-Branco G, Wagner J, Rodriguez FJ et al. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Proc. Natl Acad. Sci. USA100(22), 12747–12752 (2003).
   PubMed Web of Science ®Google Scholar
• McMahon AP, Bradley A. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell62(6), 1073–1085 (1990).
   PubMed Web of Science ®Google Scholar
• Danielian PS, McMahon AP. Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain development. Nature383(6598), 332–334 (1996).
   PubMedGoogle Scholar
• Tio M, Tan KH, Lee W, Wang TT, Udolph G. Roles of db-cAMP, IBMX and RA in aspects of neural differentiation of cord blood derived mesenchymal-like stem cells. PLoS One5(2), e9398 (2010).
   Google Scholar
• Smidt MP, Burbach JPH. How to make a mesodiencephalic dopaminergic neuron. Nat. Rev. Neurosci.8(1), 21–32 (2007).
   PubMed Web of Science ®Google Scholar
• Andersson E, Jensen JB, Parmar M, Guillemot F, Björklund A. Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2. Development133(3), 507–516 (2006).
   Google Scholar
• Saucedo-Cardenas O, Quintana-Hau JD, Le WD et al. Nurr1 is essential for the induction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons. Proc. Natl Acad. Sci. USA95(7), 4013–4018 (1998).
   PubMed Web of Science ®Google Scholar
• Smits SM, Ponnio T, Conneely OM, Burbach JPH, Smidt MP. Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons. Eur. J. Neurosci.18(7), 1731–1738 (2003).
   PubMedGoogle Scholar
• Martinat C, Bacci J-J, Leete T et al. Cooperative transcription activation by Nurr1 and Pitx3 induces embryonic stem cell maturation to the midbrain dopamine neuron phenotype. Proc. Natl Acad. Sci. USA103(8), 2874–2879 (2006).
   PubMed Web of Science ®Google Scholar
• Lee HS, Bae EJ, Yi SH et al. Foxa2 and Nurr1 synergistically yield A9 nigral dopamine neurons exhibiting improved differentiation, function, and cell survival. Stem Cells28(3), 501–512 (2010).
   Google Scholar
• Nakatani T, Kumai M, Mizuhara E, Minaki Y, Ono Y. Lmx1a and Lmx1b cooperate with Foxa2 to coordinate the specification of dopaminergic neurons and control of floor plate cell differentiation in the developing mesencephalon. Dev. Biol.339(1), 101–113 (2010).
   PubMed Web of Science ®Google Scholar
• 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.46(6), 615–631 (1989).
   PubMed Web of Science ®Google Scholar
• Barker R, Dunnett S. The biology and behaviour of intracerebral adrenal transplants in animals and man. Rev. Neurosci.4(2), 113–146 (1993).
   PubMedGoogle Scholar
• Lindvall O, Brundin P, Widner H et al. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science247(4942), 574–577 (1990).
   PubMed Web of Science ®Google Scholar
• Widner H, Tetrud J, Rehncrona S et al. Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). N. Engl. J. Med.327(22), 1556–1563 (1992).
   PubMed Web of Science ®Google Scholar
• Freed CR, Breeze RE, Rosenberg NL et al. Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson’s disease. N. Engl. J. Med.327(22), 1549–1555 (1992).
   PubMed Web of Science ®Google Scholar
• Spencer DD, Robbins RJ, Naftolin F et al. Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson’s disease. N. Engl. J. Med.327(22), 1541–1548 (1992).
   PubMed Web of Science ®Google Scholar
• Peschanski M, Defer G, N’Guyen JP et al. Bilateral motor improvement and alteration of L-dopa effect in two patients with Parkinson’s disease following intrastriatal transplantation of foetal ventral mesencephalon. Brain117(Pt 3), 487–499 (1994).
   PubMed Web of Science ®Google Scholar
• Wenning GK, Odin P, Morrish P et al. Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson’s disease. Ann. Neurol.42(1), 95–107 (1997).
   PubMed Web of Science ®Google Scholar
• Hauser RA, Freeman TB, Snow BJ et al. Long-term evaluation of bilateral fetal nigral transplantation in Parkinson disease. Arch. Neurol.56(2), 179–187 (1999).
   PubMed Web of Science ®Google Scholar
• Brundin P, Pogarell O, Hagell P et al. Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson’s disease. Brain123(Pt 7), 1380–1390 (2000).
   PubMed Web of Science ®Google Scholar
• Kordower JH, Rosenstein JM, Collier TJ et al. Functional fetal nigral grafts in a patient with Parkinson’s disease: chemoanatomic, ultrastructural, and metabolic studies. J. Comp. Neurol.370(2), 203–230 (1996).
   PubMed Web of Science ®Google Scholar
• Piccini P, Brooks DJ, Björklund A et al. Dopamine release from nigral transplants visualized in vivo in a Parkinson’s patient. Nat. Neurosci.2(12), 1137–1140 (1999).
   PubMed Web of Science ®Google Scholar
• Piccini P, Lindvall O, Björklund A et al. Delayed recovery of movement-related cortical function in Parkinson’s disease after striatal dopaminergic grafts. Ann. Neurol.48(5), 689–695 (2000).
   PubMed Web of Science ®Google Scholar
• Brundin P, Barker RA, Parmar M. Neural grafting in Parkinson’s disease Problems and possibilities. Prog. Brain Res.184, 265–294 (2010).
   PubMed Web of Science ®Google Scholar
• Clarkson ED, Zawada WM, Adams FS, Bell KP, Freed CR. Strands of embryonic mesencephalic tissue show greater dopamine neuron survival and better behavioral improvement than cell suspensions after transplantation in parkinsonian rats. Brain Res.806(1), 60–68 (1998).
   PubMed Web of Science ®Google Scholar
• Ma Y, Tang C, Chaly T et al. Dopamine cell implantation in Parkinson’s disease: long-term clinical and 18F-FDOPA PET outcomes. J. Nucl. Med.51(1), 7–15 (2010).
   PubMed Web of Science ®Google Scholar
• Olanow CW, Goetz CG, Kordower JH et al. A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann. Neurol.54(3), 403–414 (2003).
   PubMed Web of Science ®Google Scholar
• Freeman TB, Olanow CW, Hauser RA et al. Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson’s disease. Ann. Neurol.38(3), 379–388 (1995).
   PubMed Web of Science ®Google Scholar
• Olanow CW, Freeman T, Kordower J. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N. Engl. J. Med.345(2), 146; author reply 147 (2001).
   Google Scholar
• Ma Y, Feigin A, Dhawan V et al. Dyskinesia after fetal cell transplantation for parkinsonism: a PET study. Ann. Neurol.52(5), 628–634 (2002).
   PubMed Web of Science ®Google Scholar
• Politis M. Dyskinesias after neural transplantation in Parkinson’s disease: what do we know and what is next? BMC Med.8, 80 (2010).
   PubMed Web of Science ®Google Scholar
• Hagell P, Piccini P, Björklund A et al. Dyskinesias following neural transplantation in Parkinson’s disease. Nat. Neurosci.5(7), 627–628 (2002).
   PubMed Web of Science ®Google Scholar
• Hagell P, Cenci MA. Dyskinesias and dopamine cell replacement in Parkinson’s disease: a clinical perspective. Brain Res. Bull.68(1–2), 4–15 (2005).
   Google Scholar
• Piccini P, Pavese N, Hagell P et al. Factors affecting the clinical outcome after neural transplantation in Parkinson’s disease. Brain128(Pt 12), 2977–2986 (2005).
   PubMed Web of Science ®Google Scholar
• Politis M, Wu K, Loane C et al. Serotonergic neurons mediate dyskinesia side effects in Parkinson’s patients with neural transplants. Sci. Transl. Med.2(38), 38ra46 (2010).
   PubMed Web of Science ®Google Scholar
• Mendez I, Viñuela A, Astradsson A et al. Dopamine neurons implanted into people with Parkinson’s disease survive without pathology for 14 years. Nat. Med.14(5), 507–509 (2008).
   PubMed Web of Science ®Google Scholar
• Li JY, Englund E, Holton JL et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat. Med.14(5), 501–503 (2008).
   PubMed Web of Science ®Google Scholar
• Kordower JH, Chu Y, Hauser RA, Olanow CW, Freeman TB. Transplanted dopaminergic neurons develop PD pathologic changes: a second case report. Mov. Disord.23(16), 2303–2306 (2008).
   PubMed Web of Science ®Google Scholar
• Li JY, Englund E, Widner H et al. Characterization of Lewy body pathology in 12- and 16-year-old intrastriatal mesencephalic grafts surviving in a patient with Parkinson’s disease. Mov. Disord.25(8), 1091–1096 (2010).
   PubMed Web of Science ®Google Scholar