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Neurological Sciences

, Volume 34, Issue 1, pp 11–17 | Cite as

Induced pluripotent stem cells for spinal cord injury therapy: current status and perspective

  • H. Wang
  • H. FangEmail author
  • J. Dai
  • G. Liu
  • Z. J. Xu
Review Article

Abstract

Spinal cord injury (SCI) is induced by a variety of damages such as trauma, ischemia, and iatrogenic injury, resulting in sense and motion dysfunction. Despite the improvements in medical and surgical care, current treatment methods for SCI demonstrate poor and delayed efficiency, leading to different degree of permanent loss of neural function and disability in the patients. Rapid advances in stem-cells research suggest that stem cells may be applied in SCI therapy. Indeed, SCI is a major field in which stem-cell therapy has been proposed and practised, and most recently the clinical trials of stem-cell therapy were initiated, which aroused a number of clinical concerns. In this review, we summarize current status of SCI repair, then introduce the sources and biological characteristics of induced pluripotent stem cells (iPSCs), and discuss the differentiation potential of iPSCs and the perspective of the application of iPSCs in SCI therapy.

Keywords

Spinal cord injury Stem cells Induced pluripotent stem cells Transplantation therapy 

Notes

Acknowledgments

This work is supported by Talents Fund from Tongji Hospital (No. 415010299058829) and Natural Science Fund of China (No. 81071470).

Conflict of interest

The authors declare no potential conflicts of interest.

References

  1. 1.
    Salewski RP, Eftekharpour E, Fehlings MG (2010) Are induced pluripotent stem cells the future of cell-based regenerative therapies for spinal cord injury? J Cell Physiol 222:515–521PubMedGoogle Scholar
  2. 2.
    Thomas KE, Moon LD (2011) Will stem cell therapies be safe and effective for treating spinal cord injuries? Br Med Bull 98:127–142PubMedCrossRefGoogle Scholar
  3. 3.
    Illes J, Reimer JC, Kwon BK (2011) Stem cell clinical trials for spinal cord injury: readiness, reluctance, redefinition. Stem Cell Rev 7:997–1005PubMedCrossRefGoogle Scholar
  4. 4.
    Ronaghi M, Erceg S, Moreno-Manzano V et al (2010) Challenges of stem cell therapy for spinal cord injury: human embryonic stem cells, endogenous neural stem cells, or induced pluripotent stem cells? Stem Cells 28:93–99PubMedGoogle Scholar
  5. 5.
    Rowland JW, Hawryluk GW, Kwon B et al (2008) Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus 25:E2PubMedCrossRefGoogle Scholar
  6. 6.
    Hill CE, Beattie MS, Bresnahan JC (2001) Degeneration and sprouting of identified descending supraspinal axons after contusive spinal cord injury in the rat. Exp Neurol 171:153–169PubMedCrossRefGoogle Scholar
  7. 7.
    Sahni V, Kessler JA (2010) Stem cell therapies for spinal cord injury. Nat Rev Neurol 6:363–372PubMedCrossRefGoogle Scholar
  8. 8.
    Fehlings MG, Perrin RG (2006) The timing of surgical intervention in the treatment of spinal cord injury: a systematic review of recent clinical evidence. Spine (Phila Pa 1976) 31:S28–S35 (discussion S36)CrossRefGoogle Scholar
  9. 9.
    Furlan JC, Noonan V, Cadotte DW et al (2011) Timing of decompressive surgery of spinal cord after traumatic spinal cord injury: an evidence-based examination of pre-clinical and clinical studies. J Neurotrauma 28:1371–1399PubMedCrossRefGoogle Scholar
  10. 10.
    Rabchevsky AG, Patel SP, Springer JE (2011) Pharmacological interventions for spinal cord injury: where do we stand? How might we step forward? Pharmacol Ther 132:15–29PubMedCrossRefGoogle Scholar
  11. 11.
    Kwon BK, Tetzlaff W, Grauer JN et al (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 4:451–464PubMedCrossRefGoogle Scholar
  12. 12.
    Robert AA, Zamzami M, Sam AE, Al Jadid M, Al Mubarak S (2011) The efficacy of antioxidants in functional recovery of spinal cord injured rats: an experimental study. Neurol Sci (Epub ahead of print)Google Scholar
  13. 13.
    Li BC, Li Y, Chen LF et al (2011) Olfactory ensheathing cells can reduce the tissue loss but not the cavity formation in contused spinal cord of rats. J Neurol Sci 303:67–74PubMedCrossRefGoogle Scholar
  14. 14.
    Salazar DL, Uchida N, Hamers FP et al (2010) Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model. PLoS One 5:e12272PubMedCrossRefGoogle Scholar
  15. 15.
    Erceg S, Ronaghi M, Oria M et al (2010) Transplanted oligodendrocytes and motoneuron progenitors generated from human embryonic stem cells promote locomotor recovery after spinal cord transection. Stem Cells 28:1541–1549PubMedCrossRefGoogle Scholar
  16. 16.
    Tsuji O, Miura K, Okada Y et al (2010) Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc Natl Acad Sci USA 107:12704–12709PubMedCrossRefGoogle Scholar
  17. 17.
    Park HW, Lim MJ, Jung H et al (2010) Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury. Glia 58:1118–1132PubMedCrossRefGoogle Scholar
  18. 18.
    Ramon-Cueto A, Munoz-Quiles C (2011) Clinical application of adult olfactory bulb ensheathing glia for nervous system repair. Exp Neurol 229:181–194PubMedCrossRefGoogle Scholar
  19. 19.
    Xu L, Xu CJ, Lu HZ et al (2010) Long-term fate of allogeneic neural stem cells following transplantation into injured spinal cord. Stem Cell Rev 6:121–136PubMedCrossRefGoogle Scholar
  20. 20.
    Lee JH, Chung WH, Kang EH et al (2011) Schwann cell-like remyelination following transplantation of human umbilical cord blood (hUCB)-derived mesenchymal stem cells in dogs with acute spinal cord injury. J Neurol Sci 300:86–96PubMedCrossRefGoogle Scholar
  21. 21.
    Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRefGoogle Scholar
  22. 22.
    Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676PubMedCrossRefGoogle Scholar
  23. 23.
    Yu J, Vodyanik MA, Smuga-Otto K et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920PubMedCrossRefGoogle Scholar
  24. 24.
    Kim JB, Zaehres H, Wu GM et al (2008) Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 454:646–654PubMedCrossRefGoogle Scholar
  25. 25.
    Stadtfeld M, Nagaya M, Utikal J et al (2008) Induced pluripotent stem cells generated without viral integration. Science 322:945–949PubMedCrossRefGoogle Scholar
  26. 26.
    Kim JB, Sebastiano V, Wu G et al (2009) Oct4-induced pluripotency in adult neural stem cells. Cell 136:411–419PubMedCrossRefGoogle Scholar
  27. 27.
    Okita K, Nakagawa M, Hong HJ et al (2008) Generation of mouse induced pluripotent stem cells without viral vectors. Science 322:949–953PubMedCrossRefGoogle Scholar
  28. 28.
    Liao J, Wu Z, Wang Y et al (2008) Enhanced efficiency of generating induced pluripotent stem (iPS) cells from human somatic cells by a combination of six transcription factors. Cell Res 18:600–603PubMedCrossRefGoogle Scholar
  29. 29.
    Yu J, Hu K, Smuga-Otto K et al (2009) Human induced pluripotent stem cells free of vector and transgene sequences. Science 324:797–801PubMedCrossRefGoogle Scholar
  30. 30.
    Woltjen K, Michael IP, Mohseni P et al (2009) piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458:766–770PubMedCrossRefGoogle Scholar
  31. 31.
    Kaji K, Norrby K, Paca A et al (2009) Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 458:771–775PubMedCrossRefGoogle Scholar
  32. 32.
    Nagy K, Sung HK, Zhang P et al (2011) Induced pluripotent stem cell lines derived from equine fibroblasts. Stem Cell Rev 7:693–702PubMedCrossRefGoogle Scholar
  33. 33.
    Kim D, Kim CH, Moon JI et al (2009) Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 4:472–476PubMedCrossRefGoogle Scholar
  34. 34.
    Zhou H, Wu S, Joo JY et al (2009) Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4:381–384PubMedCrossRefGoogle Scholar
  35. 35.
    Shi Y, Do JT, Desponts C et al (2008) A combined chemical and genetic approach for the generation of induced pluripotent stem cells. Cell Stem Cell 2:525–528PubMedCrossRefGoogle Scholar
  36. 36.
    Zhu S, Li W, Zhou H et al (2010) Reprogramming of human primary somatic cells by OCT4 and chemical compounds. Cell Stem Cell 7:651–655PubMedCrossRefGoogle Scholar
  37. 37.
    Lyssiotis CA, Foreman RK, Staerk J et al (2009) Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4. Proc Natl Acad Sci USA 106:8912–8917PubMedCrossRefGoogle Scholar
  38. 38.
    Lin SL, Chang DC, Chang-Lin S et al (2008) Mir-302 reprograms human skin cancer cells into a pluripotent ES-cell-like state. RNA 14:2115–2124PubMedCrossRefGoogle Scholar
  39. 39.
    Anokye-Danso F, Trivedi CM, Juhr D et al (2011) Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 8:376–388PubMedCrossRefGoogle Scholar
  40. 40.
    Miyoshi N, Ishii H, Nagano H et al (2011) Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 8:633–638PubMedCrossRefGoogle Scholar
  41. 41.
    Leeb C, Jurga M, McGuckin C et al (2010) Promising new sources for pluripotent stem cells. Stem Cell Rev 6:15–26PubMedCrossRefGoogle Scholar
  42. 42.
    Wernig M, Zhao JP, Pruszak J et al (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 105:5856–5861PubMedCrossRefGoogle Scholar
  43. 43.
    Dimos JT, Rodolfa KT, Niakan KK et al (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321:1218–1221PubMedCrossRefGoogle Scholar
  44. 44.
    Ebert AD, Yu J, Rose FF Jr et al (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457:277–280PubMedCrossRefGoogle Scholar
  45. 45.
    Karumbayaram S, Novitch BG, Patterson M et al (2009) Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells 27:806–811PubMedCrossRefGoogle Scholar
  46. 46.
    Nori S, Okada Y, Yasuda A et al (2011) Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc Natl Acad Sci USA 108:16825–16830PubMedCrossRefGoogle Scholar
  47. 47.
    Zhao T, Zhang ZN, Rong Z et al (2011) Immunogenicity of induced pluripotent stem cells. Nature 474:212–215PubMedCrossRefGoogle Scholar
  48. 48.
    Keirstead HS, Nistor G, Bernal G et al (2005) Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J Neurosci 25:4694–4705PubMedCrossRefGoogle Scholar
  49. 49.
    Dolgin E (2011) Flaw in induced-stem-cell model. Nature 470:13PubMedCrossRefGoogle Scholar
  50. 50.
    Alper J (2009) Geron gets green light for human trial of ES cell-derived product. Nat Biotechnol 27:213–214PubMedCrossRefGoogle Scholar
  51. 51.
    Vierbuchen T, Ostermeier A, Pang ZP et al (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463:1035–1041PubMedCrossRefGoogle Scholar
  52. 52.
    Pang ZP, Yang N, Vierbuchen T et al (2011) Induction of human neuronal cells by defined transcription factors. Nature 476:220–223PubMedGoogle Scholar
  53. 53.
    Huang P, He Z, Ji S et al (2011) Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475:386–389PubMedCrossRefGoogle Scholar
  54. 54.
    Son EY, Ichida JK, Wainger BJ et al (2011) Conversion of mouse and human fibroblasts into functional spinal motor neurons. Cell Stem Cell 9:205–218PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

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