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. 2011 Apr 6;27(2):107. doi: 10.1007/s12264-011-1147-9

Induced pluripotent stem cells and neurodegenerative diseases

诱导多能干细胞与神经退行性疾病

Chao Chen 1,2, Shi-Fu Xiao 1,2,
PMCID: PMC5560343  PMID: 21441972

Abstract

Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and Amyotrophic Lateral Sclerosis, are characterized by idiopathic neuron loss in different regions of the central nervous system, which contributes to the relevant dysfunctions in the patients. The application of cell replacement therapy using human embryonic stem (hES) cells, though having attracted much attention, has been hampered by the intrinsic ethical problems. It has been demonstrated that adult somatic cells can be reprogrammed into the embryonic state, called induced pluripotent stem (iPS) cells. It is soon realized that iPS cells may be an alternative source for cell replacement therapy, because it raises no ethical problems and using patient-specific iPS cells for autologous transplantation will not lead to immunological rejection. What’s more, certain types of neurons derived from patient-specific iPS cells may display disease-relevant phenotypes. Thus, patientspecific iPS cells can provide a unique opportunity to directly investigate the pathological properties of relevant neural cells in individual patient, and to study the vulnerability of neural cells to pathogenic factors in vitro, which may help reveal the pathogenesis of many neurodegenerative diseases. In this review, the recent development in cellular treatment of neurodegenerative diseases using iPS cells was summarized, and the potential value of iPS cells in the modeling of neurodegenerative disease was discussed.

Keywords: neurodegenerative disease, induced pluripotent stem cell, stem cell, cell model

References

  • [1].Inoue H. Neurodegenerative disease-specific induced pluripotent stem cell research. Exp Cell Res. 2010;316:2560–2564. doi: 10.1016/j.yexcr.2010.04.022. [DOI] [PubMed] [Google Scholar]
  • [2].Thomson J.A., Itskovitz-Eldor J., Shapiro S.S., Waknitz M.A., Swiergiel J.J., Marshall V.S., et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–1147. doi: 10.1126/science.282.5391.1145. [DOI] [PubMed] [Google Scholar]
  • [3].Hanley J., Rastegarlari G., Nathwani A.C. An introduction to induced pluripotent stem cells. Br J Haematol. 2010;151:16–24. doi: 10.1111/j.1365-2141.2010.08296.x. [DOI] [PubMed] [Google Scholar]
  • [4].Chiba S., Lee Y.M., Zhou W., Freed C.R. Noggin enhances dopamine neuron production from human embryonic stem cells and improves behavioral outcome after transplantation into Parkinsonian rats. Stem Cells. 2008;26:2810–2820. doi: 10.1634/stemcells.2008-0085. [DOI] [PubMed] [Google Scholar]
  • [5].Ko J.Y., Park C.H., Koh H.C., Cho Y.H., Kyhm J.H., Kim Y.S., et al. Human embryonic stem cell-derived neural precursor as a continuous, stable, and on-demand source for human dopamine neurons. J Neurochem. 2007;103:1417–1429. doi: 10.1111/j.1471-4159.2007.04898.x. [DOI] [PubMed] [Google Scholar]
  • [6].Newman M.B., Bakay R.A. Therapeutic potential of human embryonic stem cells in Parkinson’s disease. Neurotherapeutics. 2008;5:237–251. doi: 10.1016/j.nurt.2008.02.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [7].Erceg S., Ronaghi M., Oria M., Roselló M.G., Aragó M.A., Lopez M.G., et al. Transplanted oligodendrocytes and motoneuron progenitors generated from human embryonic stem cells promote locomotor recovery after spinal cord transection. Stem Cells. 2010;28:1541–1549. doi: 10.1002/stem.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Kerr C.L., Letzen B.S., Hill C.M., Agrawal G., Thakor N.V., Sterneckert J.L., et al. Efficient differentiation of human embryonic stem cells into oligodendrocyte progenitors for application in a rat contusion model of spinal cord injury. Int J Neurosci. 2010;120:305–313. doi: 10.3109/00207450903585290. [DOI] [PubMed] [Google Scholar]
  • [9].Hicks A.U., Lappalainen R.S., Narkilahti S., Suuronen R., Corbett D., Sivenius J., et al. Transplantation of human embryonic stem cell-derived neural precursor cells and enriched environment after cortical stroke in rat: cell survival and functional recovery. Eur J Neurosci. 2009;29:562–574. doi: 10.1111/j.1460-9568.2008.06599.x. [DOI] [PubMed] [Google Scholar]
  • [10].Daadi M.M., Maag A., Steinberg G.K. Adherent self-renewable human embryonic stem cell-derived neural stem cell line: functional engraftment in experimental stroke model. PLoS One. 2008;20:e1644. doi: 10.1371/journal.pone.0001644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Song J., Lee S.T., Kang W., Park J.E., Chu K., Lee S.E., et al. Human embryonic stem cell-derived neural precursor transplants attenuate apomorphine-induced rotational behavior in rats with unilateral quinolinic acid lesions. Neurosci Lett. 2007;423:58–61. doi: 10.1016/j.neulet.2007.05.066. [DOI] [PubMed] [Google Scholar]
  • [12].Lengner C.J. iPS cell technology in regenerative medicine. Ann N Y Acad Sci. 2010;1192:38–44. doi: 10.1111/j.1749-6632.2009.05213.x. [DOI] [PubMed] [Google Scholar]
  • [13].Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676. doi: 10.1016/j.cell.2006.07.024. [DOI] [PubMed] [Google Scholar]
  • [14].Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–872. doi: 10.1016/j.cell.2007.11.019. [DOI] [PubMed] [Google Scholar]
  • [15].Wernig M., Zhao J.P., Pruszak J., Hedlund E., Fu D., Soldner F., 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 U S A. 2008;105:5856–5861. doi: 10.1073/pnas.0801677105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16].Dimos J.T., Rodolfa K.T., Niakan K.K., Weisenthal L.M., Mitsumoto H., Chung W., 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]
  • [17].Xie C.Q., Huang H., Wei S., Song L.S., Zhang J., Ritchie R.P., et al. A comparison of murine smooth cells generated from embryonic versus induced pluripotent stem cells. Stem Cells Dev. 2009;18:741–748. doi: 10.1089/scd.2008.0179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Moretti A., Bellin M., Welling A., Jung C.B., Lam J.T., Bott-Flügel L., et al. Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med. 2010;363:1397–1409. doi: 10.1056/NEJMoa0908679. [DOI] [PubMed] [Google Scholar]
  • [19].Tashiro K., Inamura M., Kawabata K., Sakurai F., Yamanishi K., Hayakawa T., et al. Efficient adipocyte and osteoblast differentiation from mouse induced pluripotent stem cells by adenoviral transduction. Stem Cells. 2009;27:1802–1811. doi: 10.1002/stem.108. [DOI] [PubMed] [Google Scholar]
  • [20].Grigoriadis A.E., Kennedy M., Bozec A., Brunton F., Stenbeck G., Park I.H., et al. Directed differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells. Blood. 2010;115:2769–2776. doi: 10.1182/blood-2009-07-234690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Okita K., Ichisaka T., Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313–317. doi: 10.1038/nature05934. [DOI] [PubMed] [Google Scholar]
  • [22].Kang L., Wang J., Zhang Y., Kou Z., Gao S. iPS cells can support fullterm development of tetraploid blastocyst-complemented embryos. Cell Stem Cell. 2009;5:135–138. doi: 10.1016/j.stem.2009.07.001. [DOI] [PubMed] [Google Scholar]
  • [23].Zhao X.Y., Li W., Lv Z., Liu L., Tong M., Hai T., et al. iPS cells produce viable mice through tetraploid complementation. Nature. 2009;461:86–90. doi: 10.1038/nature08267. [DOI] [PubMed] [Google Scholar]
  • [24].Kang L., Kou L., Zhang Y., Gao S. Induced pluripotent stem cells (iPSCs)-a new era of reprogramming. J Genet Genomics. 2010;37:415–421. doi: 10.1016/S1673-8527(09)60060-6. [DOI] [PubMed] [Google Scholar]
  • [25].Yu J., Vodyanik M.A., Smuga-Otto K., Antosiewicz-Bourget J., Frane J.L., Tian S., et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–1920. doi: 10.1126/science.1151526. [DOI] [PubMed] [Google Scholar]
  • [26].Park I.H., Zhao R., West J.A., Yabuuchi A., Huo H., Ince T.A., et al. Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 2008;451:141–146. doi: 10.1038/nature06534. [DOI] [PubMed] [Google Scholar]
  • [27].Arenas E. Towards stem cell replacement therapies for Parkinson’s disease. Biochem Biophys Res Commun. 2010;396:152–156. doi: 10.1016/j.bbrc.2010.04.037. [DOI] [PubMed] [Google Scholar]
  • [28].Sawle G.V., Bloomfield P.M., Björklund A., Brooks D.J., Brundin P., Leedners K.L., et al. Transplantation of fetal dopamine neurons in Parkinson’s disease: PET [18F]6-L-fluorodopa studies in two patients with putaminal implants. Ann Neurol. 1992;31:166–173. doi: 10.1002/ana.410310207. [DOI] [PubMed] [Google Scholar]
  • [29].Wenning G.K., Odin P., Morrish P., Rehncrona S., Wider H., Brundin P., et al. Short- and long-term survival and function of unilateral intrasriatal dopaminergic grafts in Parkinson’s disease. Ann Neurol. 1997;42:95–107. doi: 10.1002/ana.410420115. [DOI] [PubMed] [Google Scholar]
  • [30].Freed C.R., Greene P.E., Breeze R.E., Tsai W.Y., DuMouchel W., Kao R., et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med. 2001;344:710–719. doi: 10.1056/NEJM200103083441002. [DOI] [PubMed] [Google Scholar]
  • [31].Geeta R., Ramnath R.L., Rao H.S., Chandra V. One year survival and significant reversal of motor deficits in Parkinsonian rats transplanted with hESC derived dopaminergic neurons. Biochem Biophys Res Commun. 2008;373:258–264. doi: 10.1016/j.bbrc.2008.06.022. [DOI] [PubMed] [Google Scholar]
  • [32].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]
  • [33].Swistowski A., Peng J., Liu Q., Mali P., Rao M.S., Cheng L., et al. 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]
  • [34].Soldner F., Hockemeyer D., Beard C., Gao Q., Bell G.W., Cook E.G., 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]
  • [35].Hargus G., Cooper O., Deleidi M., Levy A., Lee K., Marlow E., 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 U S A. 2010;107:15921–15926. doi: 10.1073/pnas.1010209107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [36].Li J.Y., Englund E., Holton J.L., Soulet D., Hagell P., Lees A.J., et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med. 2008;14:501–503. doi: 10.1038/nm1746. [DOI] [PubMed] [Google Scholar]
  • [37].Kordower J.H., Chu Y., Hauser R.A., Freeman T.B., Olanow C.W. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson’s disease. Nat Med. 2008;14:504–506. doi: 10.1038/nm1747. [DOI] [PubMed] [Google Scholar]
  • [38].Ferri C.P., Prince M., Brayne C., Brodaty H., Fratiglioni L., Ganguli M., et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366:2112–2117. doi: 10.1016/S0140-6736(05)67889-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Minati L., Edginton T., Bruzzone M.G., Giaccone G. Current concepts in Alzheimer’s disease: a multidisciplinary review. Am J Alzheimers Dis Other Demen. 2009;24:95–121. doi: 10.1177/1533317508328602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [40].Wijesekera L.C., Leigh P.N. Amyotrophic lateral sclerosis. Orphanet J Rare Dis. 2009;4:3. doi: 10.1186/1750-1172-4-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [41].Papadeas S.T., Maragakis N.J. Advances in stem cell research for amyotrophic lateral sclerosis. Curr Opin Biotechnol. 2009;20:545–551. doi: 10.1016/j.copbio.2009.09.003. [DOI] [PubMed] [Google Scholar]
  • [42].He T.T., Zhang J.M., Shen L., Yao S.L., Tian J.H. Positron emission tomography imaging of cell transplantation in a rat model of Alzheimer’s disease. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2010;32:210–214. doi: 10.3881/j.issn.1000-503X.2010.02.017. [DOI] [PubMed] [Google Scholar]
  • [43].Wu S., Sasaki A., Yoshimoto R., Kawahara Y., Manabe T., Kataoka K., et al. Neural stem cells improve learning and memory in rats with Alzheimer’s disease. Pathobiology. 2008;75:186–194. doi: 10.1159/000124979. [DOI] [PubMed] [Google Scholar]
  • [44].Kwak Y.D., Brannen C.L., Qu T., Kim H.M., Dong X., Soba P., et al. Amyloid precursor protein regulates differentiation of human neural stem cells. Stem Cells Dev. 2006;15:381–389. doi: 10.1089/scd.2006.15.381. [DOI] [PubMed] [Google Scholar]
  • [45].Blurton-Jones M., Kitazawa M., Martinez-Coria H., Castello N.A., Müller F.J., Loring J.F., et al. Neural stem cells improve cognitive via BDNF in a transgenic model of Alzheimer disease. Proc Natl Acad Sci U S A. 2009;106:13594–13595. doi: 10.1073/pnas.0901402106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [46].Robbins R.D., Prasain N., Maier B.F., Yoder M.C., Mirmira R.G. Inducible pluripotent stem cells: not quite ready for prime time? Curr Opin Organ Transplant. 2010;15:61–67. doi: 10.1097/MOT.0b013e3283337196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [47].Skaper S.D., Giusti P. Transgenic mouse models of Parkinson’s disease and Huntington’s disease. CNS Neurol Disord Drug Targets. 2010;9:455–470. doi: 10.2174/187152710791556186. [DOI] [PubMed] [Google Scholar]

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