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Pluripotent Stem Cells for Modelling and Cell Therapy of Parkinson’s Disease

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Abstract

Studying pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD), requires adequate disease models. The available patient’s material is limited to biological fluids and post mortem brain samples. Disease modeling and drug screening can be done in animal models, although this approach has its own limitations, since laboratory animals do not suffer from many neurodegenerative diseases, including PD. The use of neurons obtained by targeted differentiation from induced pluripotent stem cells (iPSCs) with known genetic mutations, as well as from carriers of sporadic forms of the disease, will allow to elucidate new components of the molecular mechanisms of neurodegeneration. Such neuronal cultures can also serve as unique models for testing neuroprotective compounds and monitoring neurodegenerative changes against a background of various therapeutic interventions. In the future, dopaminergic neurons differentiated from iPSCs can be used for cell therapy of PD.

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Abbreviations

DNs:

dopaminergic neurons

GHSR:

growth hormone secretagogue receptor

(h)ESCs:

(human) embryonic stem cells

hfVM:

human fetal ventral mesencephalic (tissue)

iPSCs:

induced pluripotent stem cells

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PD:

Parkinson’s disease

SNCA:

α-synuclein

SNP:

single nucleotide polymorphism

References

  1. Illarioshkin, S. N. (2003) Conformational Brain Diseases [in Russian], Yanus-K, Moscow.

    Google Scholar 

  2. Levy, O. A., Malagelada, C., and Greene, L. A. (2009) Cell death pathways in Parkinson’s disease: proximal triggers, distal effectors, and final steps, Apoptosis, 14, 478–500.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Illarioshkin, S. N. (2004) Diseases of nervous system, Nervnye Bolezni, 4, 14–21.

    Google Scholar 

  4. Gardner, R. C., Burke, J. F., Nettiksimmons, J., Goldman, S., Tanner, C. M., and Yaffe, K. (2015) Traumatic brain injury in later life increases risk for Parkinson’s disease, Ann. Neurol., 77, 987–995.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lee, P. C., Bordelon, Y., Bronstein, J., and Ritz, B. (2012) Traumatic brain injury, paraquat exposure, and their relationship to Parkinson’s disease, Neurology, 79, 2061–2066.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Ratner, M. H., Farb, D. H., Ozer, J., Feldman, R. G., and Durso, R. (2014) Younger age at onset of sporadic Parkinson’s disease among subjects occupationally exposed to metals and pesticides, Interdiscip. Toxicol., 7, 123–133.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Deng, H., Wang, P., and Jankovic, J. (2018) The genetics of Parkinson’s disease, Ageing Res. Rev., 42, 72–85.

    Article  PubMed  CAS  Google Scholar 

  8. Lab of Neuroscience, The HIT Center for Life Sciences, https://doi.org/hcls.hit.edu.cn/hclsen/wabwofwweurowwcience/list.htm.

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

    Article  PubMed  CAS  Google Scholar 

  10. Rawat, N., and Singh, M. K. (2017) Induced pluripotent stem cell: a headway in reprogramming with promising approach in regenerative biology, Vet. World, 10, 640–649.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Park, I.-H., Arora, N., Huo, H., Maherali, N., Ahfeldt, T., Shimamura, A., Lensch, M. W., Cowan, C., Hochedlinger, K., and Daley, G. Q. (2008) Disease-specific induced pluripotent stem (iPS) cells, Cell, 134, 877–886.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Wernig, M., Zhao, J.-P., Pruszak, J., Hedlund, E., Fu, D., Soldner, F., Broccoli, V., Constantine-Paton, M., Isacson, O., and 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.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hargus, G., Cooper, O., Deleidi, M., Levy, A., Lee, K., Marlow, E., Yow, A., Soldner, F., Hockemeyer, D., Hallett, P. J., Osborn, T., Jaenisch, R., and 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.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Fernandez-Santiago, R., Carballo-Carbajal, I., Castellano, G., Torrent, R., Richaud, Y., Sanchez-Danes, A., Vilarrasa-Blasi, R., Sanchez-Pla, A., Mosquera, J. L., Soriano, J., Lopez-Barneo, J., Canals, J. M., Alberch, J., Raya, A., Vila, M., Consiglio, A., Martin-Subero, J. I., Ezquerra, M., and Tolosa, E. (2015) Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson’s disease patients, EMBO Mol. Med., 7, 1529–1546.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Martin, I., Kim, J. W., Dawson, V. L., and Dawson, T. M. (2014) LRRK2 pathobiology in Parkinson’s disease, J. Neurochem., 131, 554–565.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Healy, D. G., Falchi, M., O’Sullivan, S. S., Bonifati, V., Durr, A., Bressman, S., Brice, A., Aasly, J., Zabetian, C. P., Goldwurm, S., Ferreira, J. J., Tolosa, E., Kay, D. M., Klein, C., Williams, D. R., Marras, C., Lang, A. E., Wszolek, Z. K., Berciano, J., Schapira, A. H., Lynch, T., Bhatia, K. P., Gasser, T., Lees, A. J., and Wood, N. W. (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson’s disease: a case-control study, Lancet Neurol., 7, 583–590.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Liu, G.-H., Qu, J., Suzuki, K., Nivet, E., Li, M., Montserrat, N., Yi, F., Xu, X., Ruiz, S., Zhang, W., Wagner, U., Kim, A., Ren, B., Li, Y., Goebl, A., Kim, J., Soligalla, R. D., Dubova, I., Thompson, J., Yates, J., 3rd, Esteban, C. R., Sancho-Martinez, I., and Belmonte, J. C. I. (2012) Progressive degeneration of human neural stem cells caused by pathogenic LRRK2, Nature, 491, 603–607.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Seibler, P., Graziotto, J., Jeong, H., Simunovic, F., Klein, C., and Krainc, D. (2011) Mitochondrial Parkin recruitment in neurons derived from mutant PINK1 iPS cells, J. Neurosci., 31, 5970–5976.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Sanchez-Danes, A., Richaud-Patin, Y., Carballo-Carbajal, I., Jimenez-Delgado, S., Caig, C., Mora, S., Di Guglielmo, C., Ezquerra, M., Patel, B., Giralt, A., Canals, J. M., Memo, M., Alberch, J., Lopez-Barneo, J., Vila, M., Cuervo, A. M., Tolosa, E., Consiglio, A., and Raya, A. (2012) Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease, EMBO Mol. Med., 4, 380–395.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Byers, B., Cord, B., Nguyen, H. N., Schule, B., Fenno, L., Lee, P. C., Deisseroth, K., Langston, J. W., Pera, R. R., and Palmer, T. D. (2011) SNCA triplication Parkinson’s patient’s iPSC-derived DA neurons accumulate α-synuclein and are susceptible to oxidative stress, PLoS One, 6, e26159.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Chung, C. Y., Khurana, V., Auluck, P. K., Tardiff, D. F., Mazzulli, J. R., Soldner, F., Baru, V., Lou, Y., Freyzon, Y., Cho, S., Mungenast, A. E., Muffat, J., Mitalipova, M., Pluth, M. D., Jui, N. T., Schule, B., Lippard, S. J., Tsai, L. H., Krainc, D., Buchwald, S. L., Jaenisch, R., and Lindquist, S. (2013) Identification and rescue of α-synuclein toxicity in Parkinson’s patient-derived neurons, Science, 342, 983–987.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Monzel, A. S., Smits, L. M., Hemmer, K., Hachi, S., Moreno, E. L., van Wuellen, T., Jarazo, J., Walter, J., Bruggemann, I., Boussaad, I., Berger, E., Fleming, R. M. T., Bolognin, S., and Schwamborn, J. C. (2017) Derivation of human midbrain-specific organoids from neuroepithelial stem cells, Stem Cell Rep., 8, 1144–1154.

    Article  CAS  Google Scholar 

  23. Cai, J., Yang, M., Poremsky, E., Kidd, S., Schneider, J. S., and Iacovitti, L. (2010) Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats, Stem Cells Dev., 19, 1017–1023.

    Article  PubMed  CAS  Google Scholar 

  24. Martinez-Morales, P. L., and Liste, I. (2012) Stem cells as in vitro model of Parkinson’s disease, Stem Cells Int., 2012, 980941.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Doi, D., Samata, B., Katsukawa, M., Kikuchi, T., Morizane, A., Ono, Y., Sekiguchi, K., Nakagawa, M., Parmar, M., and Takahashi, J. (2014) Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation, Stem Cell Rep., 2, 337–350.

    Article  CAS  Google Scholar 

  26. Nishimura, K., Murayama, S., and Takahashi, J. (2015) Identification of neurexophilin 3 as a novel supportive factor for survival of induced pluripotent stem cell-derived dopaminergic progenitors, Stem Cells Transl. Med., 4, 932–944.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. De Boni, L., Gasparoni, G., Haubenreich, C., Tierling, S., Schmitt, I., Peitz, M., Koch, P., Walter, J., Wullner, U., and Brustle, O. (2018) DNA methylation alterations in iPSC-and hESC-derived neurons: potential implications for neurological disease modeling, Clin. Epigenetics, 10,13.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Soldner, F., Stelzer, Y., Shivalila, C. S., Abraham, B. J., Latourelle, J. C., Barrasa, M. I., Goldmann, J., Myers, R. H., Young, R. A., and Jaenisch, R. (2016) Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression, Nature, 533, 95–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Li, J. Q., Tan, L., and Yu, J. T. (2014) The role of the LRRK2 gene in parkinsonism, Mol. Neurodegener., 9,47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Pollanen, M. S., Dickson, D. W., and Bergeron, C. (1993) Pathology and biology of the Lewy body, J. Neuropathol. Exp. Neurol., 52, 183–191.

    Article  PubMed  CAS  Google Scholar 

  31. Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R., and Goedert, M. (1997) α-Synuclein in Lewy bodies, Nature, 388, 839–884.

    Article  PubMed  CAS  Google Scholar 

  32. Anderson, J. P., Walker, D. E., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J., Barbour, R., Huang, J., Kling, K., Lee, M., Diep, L., Keim, P. S., Shen, X., Chataway, T., Schlossmacher, M. G., Seubert, P., Schenk, D., Sinha, S., Gai, W. P., and Chilcote, T. J. (2006) Phosphorylation of Ser-129 is the dominant pathological modification of α-synuclein in familial and sporadic Lewy body disease, J. Biol. Chem., 281, 29739–29752.

    Article  PubMed  CAS  Google Scholar 

  33. Oueslati, A. (2016) Implication of α-synuclein phosphorylation at S129 in synucleinopathies: what have we learned in the last decade? J. Parkinson’s Dis., 6, 39–51.

    Article  CAS  Google Scholar 

  34. Alegre-Abarrategui, J., Ansorge, O., Esiri, M., and Wade-Martins, R. (2008) LRRK2 is a component of granular α-synuclein pathology in the brainstem of Parkinson’s disease, Neuropathol. Appl. Neurobiol., 34, 272–283.

    Article  PubMed  CAS  Google Scholar 

  35. Martin, I., Dawson, V. L., and Dawson, T. M. (2011) Recent advances in the genetics of Parkinson’s disease, Annu. Rev. Genomics Hum. Genet., 12, 301–325.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Qing, X., Walter, J., Jarazo, J., Arias-Fuenzalida, J., Hillje, A. L., and Schwamborn, J. C. (2017) CRISPR/Cas9 and piggyBac-mediated footprint-free LRRK2-G2019S knock-in reveals neuronal complexity phenotypes and α-synucle-in modulation in dopaminergic neurons, Stem Cell Res., 24, 44–50.

    Article  PubMed  CAS  Google Scholar 

  37. Ferreia, M., and Massano, J. (2017) An updated review of Parkinson’s disease genetics and clinicopathological correlations, Acta Neurol. Scand., 135, 273–284.

    Article  Google Scholar 

  38. Abizaid, A., Liu, Z. W., Andrews, Z. B., Shanabrough, M., Borok, E., Elsworth, J. D., Roth, R. H., Sleeman, M. W., Picciotto, M. R., Tschop, M. H., Gao, X. B., and Horvath, T. L. (2006) Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite, J. Clin. Invest., 116, 3229–3239.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Diano, S., Farr, S. A., Benoit, S. C., McNay, E. C., da Silva, I., Horvath, B., Gaskin, F. S., Nonaka, N., Jaeger, L. B., Banks, W. A., Morley, J. E., Pinto, S., Sherwin, R. S., Xu, L., Yamada, K. A., Sleeman, M. W., Tschop, M. H., and Horvath, T. L. (2006) Ghrelin controls hippocampal spine synapse density and memory performance, Nat. Neurosci., 9, 381–388.

    Article  PubMed  CAS  Google Scholar 

  40. Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., and Kangawa, K. (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach, Nature, 402, 656–660.

    Article  PubMed  CAS  Google Scholar 

  41. Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., and Matsukura, S. (2001) A role for ghrelin in the central regulation of feeding, Nature, 409, 194–198.

    Article  PubMed  CAS  Google Scholar 

  42. Cowley, M. A., Smith, R. G., Diano, S., Tschop, M., Pronchuk, N., Grove, K. L., Strasburger, C. J., Bidlingmaier, M., Esterman, M., Heiman, M. L., Garcia-Segura, L. M., Nillni, E. A., Mendez, P., Low, M. J., Sotonyi, P., Friedman, J. M., Liu, H., Pinto, S., Colmers, W. F., Cone, R. D., and Horvath, T. L. (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis, Neuron, 37, 649–661.

    Article  PubMed  CAS  Google Scholar 

  43. Shi, L., Bian, X., Qu, Z., Ma, Z., Zhou, Y., Wang, K., Jiang, H., and Xie, J. (2013) Peptide hormone ghrelin enhances neuronal excitability by inhibition of Kv7/KCNQ channels, Nat. Commun., 4, 1435.

    Article  PubMed  CAS  Google Scholar 

  44. Suda, Y., Kuzumaki, N., Sone, T., Narita, M., Tanaka, K., Hamada, Y., Iwasawa, C., Shibasaki, M., Maekawa, A., Matsuo, M., Akamatsu, W., Hattori, N., Okano, H., and Narita, M. (2018) Down-regulation of ghrelin receptors on dopaminergic neurons in the substantia nigra contributes to Parkinson’s disease-like motor dysfunction, Mol. Brain, 11,6.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Brundin, P., Strecker, R. E., Lindvall, O., Isacson, O., Nilsson, O. G., Barbin, G., Prochiantz, A., Forni, C., Nieoullon, A., Widner, H., Gage, F. H., and Bjorklund, A. (1987) Intracerebral grafting of dopamine neurons. Experimental basis for clinical trials in patients with Parkinson’s disease, Ann. N. Y. Acad. Sci., 495, 473–496.

    Article  PubMed  CAS  Google Scholar 

  46. Barker, R. A., Drouin-Ouellet, J., and Parmar, M. (2015) Cell-based therapies for Parkinson’s disease-past insights and future potential, Nat. Rev. Neurol., 11, 492–503.

    Article  PubMed  CAS  Google Scholar 

  47. Barker, R. A., Parmar, M., Studer, L., and Takahashi, J. (2017) Human trials of stem cell-derived dopamine neurons for Parkinson’s disease: dawn of a new era, Cell Stem Cell, 21, 569–573.

    Article  PubMed  CAS  Google Scholar 

  48. Shimohama, S., Sawada, H., Kitamura, Y., and Taniguchi, T. (2003) Disease model: Parkinson’s disease, Trends Mol. Med., 9, 360–365.

    Article  PubMed  CAS  Google Scholar 

  49. Saiki, H., Hayashi, T., Takahashi, R., and Takahashi, J. (2010) Objective and quantitative evaluation of motor function in a monkey model of Parkinson’s disease, J. Neurosci. Methods, 190, 198–204.

    Article  PubMed  CAS  Google Scholar 

  50. 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. (2005) Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson’s primate model, J. Clin. Invest., 115, 102–109.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Lebedeva, O. S., Lagar’kova, M. A., Kiselev, S. L., Mukhina, I. V., Vedunova, M. V., Usova, O. V., Stavrovskaya, A. V., Yamshchikova, N. G., Fedotova, E. Yu., Grivennikov, I. A., Khaspekov, L. G., and Illarioshkin, S. N. (2013) Morphofunctional properties of induced pluripotent stem cells derived from human skin fibroblasts and differentiated to dopaminergic neurons, Neirokhimiya, 3, 233–241.

    Google Scholar 

  52. Doi, D., Morizane, A., Kikuchi, T., Onoe, H., Hayashi, T., Kawasaki, T., Motono, M., Sasai, Y., Saiki, H., Gomi, M., Yoshikawa, T., Hayashi, H., Shinoyama, M., Refaat, M. M., Suemori, H., Miyamoto, S., and Takahashi, J. (2012) Prolonged maturation culture favors a reduction in the tumorigenicity and the dopaminergic function of human ESC-derived neural cells in a primate model of Parkinson’s disease, Stem Cells, 30, 935–945.

    Article  PubMed  CAS  Google Scholar 

  53. Kikuchi, T., Morizane, A., Doi, D., Onoe, H., Hayashi, T., Kawasaki, T., Saiki, H., Miyamoto, S., and Takahashi, J. (2011) Survival of human induced pluripotent stem cell-derived midbrain dopaminergic neurons in the brain of a primate model of Parkinson’s disease, J. Parkinson’s Dis., 1, 395–412.

    CAS  Google Scholar 

  54. Kikuchi, T., Morizane, A., Doi, D., Magotani, H., Onoe, H., Hayashi, T., Mizuma, H., Takara, S., Takahashi, R., Inoue, H., Morita, S., Yamamoto, M., Okita, K., Nakagawa, M., Parmar, M., and Takahashi, J. (2017) Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model, Nature, 548, 592–596.

    Article  PubMed  CAS  Google Scholar 

  55. Morizane, A., Doi, D., Kikuchi, T., Okita, K., Hotta, A., Kawasaki, T., Hayashi, T., Onoe, H., Shiina, T., Yamanaka, S., and Takahashi, J. (2013) Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate, Stem Cell Rep., 1, 283–292.

    Article  CAS  Google Scholar 

  56. Okita, K., Matsumura, Y., Sato, Y., Okada, A., Morizane, A., Okamoto, S., Hong, H., Nakagawa, M., Tanabe, K., Tezuka, K., Shibata, T., Kunisada, T., Takahashi, M., Takahashi, J., Saji, H., and Yamanaka, S. (2011) A more efficient method to generate integration-free human iPS cells, Nat. Methods, 8, 409–412.

    Article  PubMed  CAS  Google Scholar 

  57. Mandai, M., Watanabe, A., Kurimoto, Y., Hirami, Y., Morinaga, C., Daimon, T., Fujihara, M., Akimaru, H., Sakai, N., Shibata, Y., Terada, M., Nomiya, Y., Tanishima, S., Nakamura, M., Kamao, H., Sugita, S., Onishi, A., Ito, T., Fujita, K., Kawamata, S., Go, M. J., Shinohara, C., Hata, K. I., Sawada, M., Yamamoto, M., Ohta, S., Ohara, Y., Yoshida, K., Kuwahara, J., Kitano, Y., Amano, N., Umekage, M., Kitaoka, F., Tanaka, A., Okada, C., Takasu, N., Ogawa, S., Yamanaka, S., and Takahashi, M. (2017) Autologous induced stem-cell-derived retinal cells for macular degeneration, N. Engl. J. Med., 376, 1038–1046.

    Article  PubMed  CAS  Google Scholar 

  58. Li, W., Englund, E., Winder, H., Mattsson, B., van Westen, D., Latt, D., Rehncrona, S., Brundin, P., Bjorklund, A., Lindvall, O., and Li, J. Y. (2016) Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain, Proc. Natl. Acad. Sci. USA, 113, 6544–6549.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  59. Morizane, A., and Takahashi, J. (2016) Cell therapy for Parkinson’s disease, Neurol. Med. Chir. (Tokyo), 56, 102–109.

    Article  Google Scholar 

  60. Grealish, S., Diguet, E., Kirkeby, A., Mattsson, B., Heuer, A., Bramoulle, Y., Van Camp, N., Perrier, A. L., Hantraye, P., Bjorklund, A., and Parmar, M. (2014) Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson’s disease, Cell Stem Cell, 15, 653–665.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Kirkeby, A., Grealish, S., Wolf, D. A., Nelander, J., Wood, J., Lundblad, M., Lindvall, O., and Parmar, M. (2012) Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions, Cell Rep., 1, 703–714.

    Article  PubMed  CAS  Google Scholar 

  62. Kriks, S., Shim, J.-W., Piao, J., Ganat, Y. M., Wakeman, D. R., Xie, Z., Carrillo-Reid, L., Auyeung, G., Antonacci, C., Buch, A., Yang, L., Beal, M. F., Surmeier, D. J., Kordower, J. H., Tabar, V., and Studer, L. (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease, Nature, 480, 547–553.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Steinbeck, J. A., Choi, S. J., Mrejeru, A., Ganat, Y., Deisseroth, K., Sulzer, D., Mosharov, E. V., and Stude, L. (2015) Optogenetics enables functional analysis of human embryonic stem cell-derived grafts in a Parkinson’s disease model, Nat. Biotechnol., 33, 204–209.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Andrews, P. W., Ben-David, U., Benvenisty, N., Coffey, P., Eggan, K., Knowles, B. B., Nagy, A., Pera, M., Reubinoff, B., Rugg-Gunn, P. J., and Stacey, G. N. (2017) Assessing the safety of human pluripotent stem cells and their derivatives for clinical applications, Stem Cell Rep., 9, 1–4.

    Article  Google Scholar 

  65. Barker, R. A., Parmar, M., Kirkeby, A., Bjorklund, A., Thompson, L., and Brundin, P. (2016) Are stem cell-based therapies for Parkinson’s disease ready for the clinic in 2016? J. Parkinson’s Dis., 6, 57–63.

    Article  Google Scholar 

  66. Cyranoski, D. (2017) Trials of embryonic stem cells to launch in China, Nature, 546, 15–16.

    Article  PubMed  CAS  Google Scholar 

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  1. Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, 119435, Moscow, Russia

    O. S. Lebedeva & M. A. Lagarkova

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Original Russian Text © O. S. Lebedeva, M. A. Lagarkova, 2018, published in Biokhimiya, 2018, Vol. 83, No. 9, pp. 1318–1330.

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Lebedeva, O.S., Lagarkova, M.A. Pluripotent Stem Cells for Modelling and Cell Therapy of Parkinson’s Disease. Biochemistry Moscow 83, 1046–1056 (2018). https://doi.org/10.1134/S0006297918090067

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