Skip to main content
NCBI home page
Protein & Cell logoLink to Protein & Cell
. 2012 Mar 11;3(2):91–97. doi: 10.1007/s13238-012-2029-2

Converted neural cells: induced to a cure?

Weiqi Zhang 1, Shunlei Duan 1, Ying Li 1, Xiuling Xu 1, Jing Qu 1,✉, Weizhou Zhang 2,✉, Guang-Hui Liu 1,✉
PMCID: PMC4104580  NIHMSID: NIHMS593536  PMID: 22410787

Abstract

Many neurodegenerative disorders such as Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and others often occur as a result of progressive loss of structure or function of neurons. Recently, many groups were able to generate neural cells, either differentiated from induced pluripotent stem cells (iPSCs) or converted from somatic cells. Advances in converted neural cells have opened a new era to ease applications for modeling diseases and screening drugs. In addition, the converted neural cells also hold the promise for cell replacement therapy (Kikuchi et al., 2011; Krencik et al., 2011; Kriks et al., 2011; Nori et al., 2011; Rhee et al., 2011; Schwartz et al., 2012). Here we will mainly discuss most recent progress on using converted functional neural cells to treat neurological diseases and highlight potential clinical challenges and future perspectives.

Keywords: converted neural cell, pluripotent stem cell, transdifferentiation, transplantation, neurodegenerative diseases

Footnotes

These authors contributed equally to the work.

Contributor Information

Jing Qu, Email: jqu@salk.edu.

Weizhou Zhang, Email: w4zhang@ucsd.edu.

Guang-Hui Liu, Email: ghliu@ibp.ac.cn.

References

  1. Barrilleaux B., Knoepfler P.S. Inducing iPSCs to escape the dish. Cell Stem Cell. 2011;9:103–111. doi: 10.1016/j.stem.2011.07.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berke J.D., Hyman S.E. Addiction, dopamine, and the molecular mechanisms of memory. Neuron. 2000;25:515–532. doi: 10.1016/S0896-6273(00)81056-9. [DOI] [PubMed] [Google Scholar]
  3. Bjorklund L.M., Sanchez-Pernaute R., Chung S., Andersson T., Chen I.Y., McNaught K.S., Brownell A.L., Jenkins B.G., Wahlestedt C., Kim K.S., et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA. 2002;99:2344–2349. doi: 10.1073/pnas.022438099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boillee S., Vande Velde C., Cleveland D.W. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron. 2006;52:39–59. doi: 10.1016/j.neuron.2006.09.018. [DOI] [PubMed] [Google Scholar]
  5. Brennand K.J., Simone A., Jou J., Gelboin-Burkhart C., Tran N., Sangar S., Li Y., Mu Y., Chen G., Yu D., et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature. 2011;473:221–225. doi: 10.1038/nature09915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cai J., Yang M., Poremsky E., Kidd S., Schneider J.S., Iacovitti L. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats. Stem Cells Dev. 2010;19:1017–1023. doi: 10.1089/scd.2009.0319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Caiazzo M., Dell’Anno M.T., Dvoretskova E., Lazarevic D., Taverna S., Leo D., Sotnikova T.D., Menegon A., Roncaglia P., Colciago G., et al. Direct generation of functional dopaminergic neurons from mouse and human fibroblasts. Nature. 2011;476:224–227. doi: 10.1038/nature10284. [DOI] [PubMed] [Google Scholar]
  8. Chen S.J., Chang C.M., Tsai S.K., Chang Y.L., Chou S.J., Huang S.S., Tai L.K., Chen Y.C., Ku H.H., Li H.Y., et al. Functional improvement of focal cerebral ischemia injury by subdural transplantation of induced pluripotent stem cells with fibrin glue. Stem Cells Dev. 2010;19:1757–1767. doi: 10.1089/scd.2009.0452. [DOI] [PubMed] [Google Scholar]
  9. Cleveland D.W., Rothstein J.D. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci. 2001;2:806–819. doi: 10.1038/35097565. [DOI] [PubMed] [Google Scholar]
  10. Davis H., Guo X., Lambert S., Stancescu M., Hickman J.J. Small molecule induction of human umbilical stem cells into myelin basic protein positive oligodendrocytes in a defined three-dimensional environment. ACS Chemical Neuroscience. 2011;3:31–39. doi: 10.1021/cn200082q. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Deleidi M., Hargus G., Hallett P., Osborn T., Isacson O. Development of histocompatible primate-induced pluripotent stem cells for neural transplantation. Stem Cells. 2011;29:1052–1063. doi: 10.1002/stem.662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Devine M.J., Ryten M., Vodicka P., Thomson A.J., Burdon T., Houlden H., Cavaleri F., Nagano M., Drummond N.J., Taanman J.W., et al. Parkinson’s disease induced pluripotent stem cells with triplication of the alpha-synuclein locus. Nat Commun. 2011;2:440. doi: 10.1038/ncomms1453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dimos J.T., Rodolfa K.T., Niakan K.K., Weisenthal L.M., Mitsumoto H., Chung W., Croft G.F., Saphier G., Leibel R., Goland R., et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008;321:1218–1221. doi: 10.1126/science.1158799. [DOI] [PubMed] [Google Scholar]
  14. Dolmetsch R., Geschwind D.H. The human brain in a dish: the promise of iPSC-derived neurons. Cell. 2011;145:831–834. doi: 10.1016/j.cell.2011.05.034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Donnan G.A., Fisher M., Macleod M., Davis S.M. Stroke. Lancet. 2008;371:1612–1623. doi: 10.1016/S0140-6736(08)60694-7. [DOI] [PubMed] [Google Scholar]
  16. Ebert A.D., Yu J., Rose F.F., Jr, Mattis V.B., Lorson C.L., Thomson J.A., Svendsen C.N. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature. 2009;457:277–280. doi: 10.1038/nature07677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fujioka T., Shimizu N., Yoshino K., Miyoshi H., Nakamura Y. Establishment of induced pluripotent stem cells from human neonatal tissues. Human cell. Off J Human Cell Res Soc. 2010;23:113–118. doi: 10.1111/j.1749-0774.2010.00091.x. [DOI] [PubMed] [Google Scholar]
  18. Grskovic M., Javaherian A., Strulovici B., Daley G.Q. Induced pluripotent stem cells—opportunities for disease modelling and drug discovery. Nat Rev Drug Discov. 2011;10:915–929. doi: 10.1038/nrd3577. [DOI] [PubMed] [Google Scholar]
  19. Han S.S., Williams L.A., Eggan K.C. Constructing and deconstructing stem cell models of neurological disease. Neuron. 2011;70:626–644. doi: 10.1016/j.neuron.2011.05.003. [DOI] [PubMed] [Google Scholar]
  20. Hargus G., Cooper O., Deleidi M., Levy A., Lee K., Marlow E., Yow A., Soldner F., Hockemeyer D., Hallett P.J., et al. 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. 2010;107:15921–15926. doi: 10.1073/pnas.1010209107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hayashi K., Hashimoto M., Koda M., Naito A.T., Murata A., Okawa A., Takahashi K., Yamazaki M. Increase of sensitivity to mechanical stimulus after transplantation of murine induced pluripotent stem cell-derived astrocytes in a rat spinal cord injury model. J Neurosurg Spine. 2011;15:582–593. doi: 10.3171/2011.7.SPINE10775. [DOI] [PubMed] [Google Scholar]
  22. Hockemeyer D., Jaenisch R. Gene targeting in human pluripotent cells. Cold Spring Harb Symp Quant Biol. 2010;75:201–209. doi: 10.1101/sqb.2010.75.021. [DOI] [PubMed] [Google Scholar]
  23. Huse D.M., Schulman K., Orsini L., Castelli-Haley J., Kennedy S., Lenhart G. Burden of illness in Parkinson’s disease. Movement disorders. Off J Move Dis Soc. 2005;20:1449–1454. doi: 10.1002/mds.20609. [DOI] [PubMed] [Google Scholar]
  24. Ilieva H., Polymenidou M., Cleveland D.W. Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol. 2009;187:761–772. doi: 10.1083/jcb.200908164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Israel M.A., Yuan S.H., Bardy C., Reyna S.M., Mu Y., Herrera C., Hefferan M.P., Van Gorp S., Nazor K.L., Boscolo F.S., et al. Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature. 2012;482:216–220. doi: 10.1038/nature10821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jensen, M.B., Yan, H., Krishnaney-Davison, R., Al Sawaf, A., and Zhang, S.C. (2011). Survival and differentiation of transplanted neural stem cells derived from human induced pluripotent stem cells in a rat stroke model. J Stroke Cerebrovasc Dis: the official journal of National Stroke Association. [DOI] [PMC free article] [PubMed]
  27. Karumbayaram S., Novitch B.G., Patterson M., Umbach J.A., Richter L., Lindgren A., Conway A.E., Clark A.T., Goldman S.A., Plath K., et al. Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells. 2009;27:806–811. doi: 10.1002/stem.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kawai H., Yamashita T., Ohta Y., Deguchi K., Nagotani S., Zhang X., Ikeda Y., Matsuura T., Abe K. Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain. J Cerebral Blood Flow Met: official journal of the International Society of Cerebral Blood Flow and Metabolism. 2010;30:1487–1493. doi: 10.1038/jcbfm.2010.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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, 395-412. [DOI] [PubMed]
  30. Kim H.W., Svendsen C.N. Gene editing in stem cells hits the target. Cell Stem Cell. 2011;9:93–94. doi: 10.1016/j.stem.2011.07.011. [DOI] [PubMed] [Google Scholar]
  31. Kim J., Efe J.A., Zhu S., Talantova M., Yuan X., Wang S., Lipton S.A., Zhang K., Ding S. Direct reprogramming of mouse fibroblasts to neural progenitors. Proc Natl Acad Sci USA. 2011;108:7838–7843. doi: 10.1073/pnas.1103113108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kim J., Su S.C., Wang H., Cheng A.W., Cassady J.P., Lodato M.A., Lengner C.J., Chung C.Y., Dawlaty M.M., Tsai L.H., et al. Functional integration of dopaminergic neurons directly converted from mouse fibroblasts. Cell Stem Cell. 2011;9:413–419. doi: 10.1016/j.stem.2011.09.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kim J.H., Auerbach J.M., Rodriguez-Gomez J.A., Velasco I., Gavin D., Lumelsky N., Lee S.H., Nguyen J., Sanchez-Pernaute R., Bankiewicz K., et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson’s disease. Nature. 2002;418:50–56. doi: 10.1038/nature00900. [DOI] [PubMed] [Google Scholar]
  34. Kim K.Y., Hysolli E., Park I.H. Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc Natl Acad Sci USA. 2011;108:14169–14174. doi: 10.1073/pnas.1018979108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Koch P., Breuer P., Peitz M., Jungverdorben J., Kesavan J., Poppe D., Doerr J., Ladewig J., Mertens J., Tuting T., et al. Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease. Nature. 2011;480:543–546. doi: 10.1038/nature10671. [DOI] [PubMed] [Google Scholar]
  36. Krencik R., Weick J.P., Liu Y., Zhang Z.J., Zhang S.C. Specification of transplantable astroglial subtypes from human pluripotent stem cells. Nat Biotechnol. 2011;29:528–534. doi: 10.1038/nbt.1877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kriks S., Shim J.W., Piao J., Ganat Y.M., Wakeman D.R., Xie Z., Carrillo-Reid L., Auyeung G., Antonacci C., Buch A., et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature. 2011;480:547–551. doi: 10.1038/nature10648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lee S.T., Chu K., Jung K.H., Song Y.M., Jeon D., Kim S.U., Kim M., Lee S.K., Roh J.K. Direct generation of neurosphere-like cells from human dermal fibroblasts. PLoS ONE. 2011;6:e21801. doi: 10.1371/journal.pone.0021801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lindvall O., Björklund A. Cell therapeutics in Parkinson’s disease. Neurotherapeutics. 2011;8:539–548. doi: 10.1007/s13311-011-0069-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Liu G.H., Sancho-Martinez I., Izpisua Belmonte J.C. Cut and Paste: restoring cellular function by gene correction. Ce Res. 2012;22:283–284. doi: 10.1038/cr.2011.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Liu G.H., Suzuki K., Qu J., Sancho-Martinez I., Yi F., Li M., Kumar S., Nivet E., Kim J., Soligalla R.D., et al. Targeted gene correction of laminopathy-associated LMNA mutations in patient-specific iPSCs. Cell Stem Cell. 2011;8:688–694. doi: 10.1016/j.stem.2011.04.019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Liu X., Li F., Stubblefield E.A., Blanchard B., Richards T.L., Larson G.A., He Y., Huang Q., Tan A.C., Zhang D., et al. Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Res. 2012;22:321–332. doi: 10.1038/cr.2011.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lujan, E., Chanda, S., Ahlenius, H., Sudhof, T.C., and Wernig, M. (2012). Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proc National Acad Sci USA. doi: 10.1073/pnas.1121003109. [DOI] [PMC free article] [PubMed]
  44. Marchetto M.C., Carromeu C., Acab A., Yu D., Yeo G.W., Mu Y., Chen G., Gage F.H., Muotri A.R. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell. 2010;143:527–539. doi: 10.1016/j.cell.2010.10.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Nguyen H.N., Byers B., Cord B., Shcheglovitov A., Byrne J., Gujar P., Kee K., Schüle B., Dolmetsch R.E., Langston W., et al. LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell. 2011;8:267–280. doi: 10.1016/j.stem.2011.01.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Nori S., Okada Y., Yasuda A., Tsuji O., Takahashi Y., Kobayashi Y., Fujiyoshi K., Koike M., Uchiyama Y., Ikeda E., et al. Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc Natl Acad Sci USA. 2011;108:16825–16830. doi: 10.1073/pnas.1108077108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Pan H., Zhang W., Liu G.H. Find and replace: editing human genome in pluripotent stem cells. Protein Cell. 2011;2:950–956. doi: 10.1007/s13238-011-1132-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Park I.H., Arora N., Huo H., Maherali N., Ahfeldt T., Shimamura A., Lensch M.W., Cowan C., Hochedlinger K., Daley G.Q. Disease-specific induced pluripotent stem cells. Cell. 2008;134:877–886. doi: 10.1016/j.cell.2008.07.041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Pasca S.P., Portmann T., Voineagu I., Yazawa M., Shcheglovitov A., Pasca A.M., Cord B., Palmer T.D., Chikahisa S., Nishino S., et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med. 2011;17:1657–1662. doi: 10.1038/nm.2576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Pawitan J.A. Prospect of cell therapy for Parkinson’s disease. Anat Cell Biol. 2011;44:256–264. doi: 10.5115/acb.2011.44.4.256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Pfisterer U., Kirkeby A., Torper O., Wood J., Nelander J., Dufour A., Bjorklund A., Lindvall O., Jakobsson J., Parmar M. Direct conversion of human fibroblasts to dopaminergic neurons. Proc Natl Acad Sci USA. 2011;108:10343–10348. doi: 10.1073/pnas.1105135108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Qiang L., Fujita R., Yamashita T., Angulo S., Rhinn H., Rhee D., Doege C., Chau L., Aubry L., Vanti W.B., et al. Directed conversion of Alzheimer’s disease patient skin fibroblasts into functional neurons. Cell. 2011;146:359–371. doi: 10.1016/j.cell.2011.07.007. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  53. Rhee Y.-H., Ko J.-Y., Chang M.-Y., Yi S.-H., Kim D., Kim C.-H., Shim J.-W., Jo A.Y., Kim B.-W., Lee H., et al. Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease. J Clin Invest. 2011;121:2326–2335. doi: 10.1172/JCI45794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Ross C.A., Poirier M.A. Protein aggregation and neurodegenerative disease. Nat Med. 2004;10:S10–S17. doi: 10.1038/nm1066. [DOI] [PubMed] [Google Scholar]
  55. Roy N.S., Cleren C., Singh S.K., Yang L., Beal M.F., Goldman S.A. Functional engraftment of human ES cell-derived dopaminergic neurons enriched by coculture with telomerase-immortalized midbrain astrocytes. Nat Med. 2006;12:1259–1268. doi: 10.1038/nm1495. [DOI] [PubMed] [Google Scholar]
  56. Sanchez-Pernaute R., Lee H., Patterson M., Reske-Nielsen C., Yoshizaki T., Sonntag K.C., Studer L., Isacson O. Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson’s disease. Brain: a journal of neurology. 2008;131:2127–2139. doi: 10.1093/brain/awn144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Schwartz, S.D., Hubschman, J.P., Heilwell, G., Franco-Cardenas, V., Pan, C.K., Ostrick, R.M., Mickunas, E., Gay, R., Klimanskaya, I., and Lanza, R. (2012). Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet. Lancet. 2012 Jan 24 [Epub ahead of print]. [DOI] [PubMed]
  58. Seifinejad A., Tabebordbar M., Baharvand H., Boyer L.A., Salekdeh G.H. Progress and promise towards safe induced pluripotent stem cells for therapy. Stem Cell Rev. 2010;6:297–306. doi: 10.1007/s12015-010-9121-x. [DOI] [PubMed] [Google Scholar]
  59. Soldner F., Hockemeyer D., Beard C., Gao Q., Bell G.W., Cook E.G., Hargus G., Blak A., Cooper O., Mitalipova M., et al. Parkinson’s disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell. 2009;136:964–977. doi: 10.1016/j.cell.2009.02.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Son E.Y., Ichida J.K., Wainger B.J., Toma J.S., Rafuse V.F., Woolf C.J., Eggan K. Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell. 2011;9:205–218. doi: 10.1016/j.stem.2011.07.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Swistowski A., Peng J., Liu Q., Mali P., Rao M.S., Cheng L., Zeng X. Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions. Stem Cells. 2010;28:1893–1904. doi: 10.1002/stem.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Tsuji O., Miura K., Okada Y., Fujiyoshi K., Mukaino M., Nagoshi N., Kitamura K., Kumagai G., Nishino M., Tomisato S., et al. Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc Natl Acad Sci USA. 2010;107:12704–12709. doi: 10.1073/pnas.0910106107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Varela C., Denis J.A., Polentes J., Feyeux M., Aubert S., Champon B., Pietu G., Peschanski M., Lefort N. Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells. J Clin Invest. 2012;122:569–574. doi: 10.1172/JCI46268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Vierbuchen T., Ostermeier A., Pang Z.P., Kokubu Y., Sudhof T.C., Wernig M. Direct conversion of fibroblasts to functional neurons by defined factors. Nature. 2010;463:1035–1041. doi: 10.1038/nature08797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Wernig M., Benninger F., Schmandt T., Rade M., Tucker K.L., Bussow H., Beck H., Brustle O. Functional integration of embryonic stem cell-derived neurons in vivo. J Neurosci: the official journal of the Society for Neuroscience. 2004;24:5258–5268. doi: 10.1523/JNEUROSCI.0428-04.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Wernig M., Zhao J.-P., Pruszak J., Hedlund E., Fu D., Soldner F., Broccoli V., Constantine-Paton M., Isacson O., 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. 2008;105:5856–5861. doi: 10.1073/pnas.0801677105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Yagi T., Ito D., Okada Y., Akamatsu W., Nihei Y., Yoshizaki T., Yamanaka S., Okano H., Suzuki N. Modeling familial Alzheimer’s disease with induced pluripotent stem cells. Human Mol Genet. 2011;20:4530–45839. doi: 10.1093/hmg/ddr394. [DOI] [PubMed] [Google Scholar]
  68. Yamashita T., Kawai H., Tian F., Ohta Y., Abe K. Tumorigenic development of induced pluripotent stem cells in ischemic mouse brain. Cell Transplant. 2011;20:883–891. doi: 10.3727/096368910X539092. [DOI] [PubMed] [Google Scholar]
  69. Yang D., Zhang Z.J., Oldenburg M., Ayala M., Zhang S.C. Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats. Stem Cells. 2008;26:55–63. doi: 10.1634/stemcells.2007-0494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Zhang W., Ding Z., Liu G.H. Evolution of iPSC disease models. Protein Cell. Protein Cell. 2012;3:1–4. doi: 10.1007/s13238-012-2005-x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Protein & Cell are provided here courtesy of Oxford University Press

RESOURCES