Skip to main content

Advertisement

SpringerLink
Log in

Differentiation of Oligodendrocytes from Mouse Induced Pluripotent Stem Cells Without Serum

  • Original Article
  • Published:
Translational Stroke Research Aims and scope Submit manuscript

Abstract

Cell therapy using induced pluripotent stem (iPS) cells might become a new approach for treating neonatal hypoxic–ischemic injury such as periventricular leukomalacia. To obtain appropriate donor cells for transplantation, we differentiated oligodendrocyte (OL) lineage cells from mouse iPS cells. Induction of OL lineage cell differentiation from iPS cells was carried out with a seven-step culture method. Mouse iPS cells (stage 1) were induced to form embryoid bodies for 4 days under a serum-free condition that was suitable for ectoderm induction (stage 2), following by selection of nestin-positive neural stem cells (NSCs) for 10–12 days (stage 3). NSCs were cultured in expansion medium containing fibroblast growth factor (FGF)-2 for 4 days (stage 4), induced to differentiate into glial progenitor cells by epidermal growth factor and fibroblast growth factor (FGF-2) treatment for 4–5 days (stage 5), and then into OL progenitor cells by culture in neurobasal A medium containing FGF-2 and platelet-derived growth factor for 6–8 days (stage 6). Terminal differentiation into O4-positive OLs was carried out by culture in neurobasal A containing T3 and ciliary neurotrophic factor for 7 days (stage 7). Inwardly rectifying K+ currents, which are characteristic of OLs, were detected in iPS cell-derived cells at stage 7 in whole cell clamp mode. Our data suggest that OLs can be effectively differentiated from mouse iPS cells without serum in a stepwise manner, which may be appropriate for use as donor cells in transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR. Neurologic and developmental disability after extremely preterm birth. Epicure study group. N Engl J Med. 2000;343:378–84.

    Article  PubMed  CAS  Google Scholar 

  2. Back SA, Rivkees SA. Emerging concepts in periventricular white matter injury. Semin Perinatol. 2004;28:405–14.

    Article  PubMed  Google Scholar 

  3. Fujimoto S, Togari H, Takashima S, Funato M, Yoshioka H, Ibara S, Tatsuno M. National survey of periventricular leukomalacia in Japan. Acta Paediatr Jpn. 1998; 239–43.

  4. Volpe JJ. Neurobiology of periventricular leukomalacia in the premature infant. Pediatr Res. 2001;50:553–62.

    Article  PubMed  CAS  Google Scholar 

  5. Back SA, Luo NL, Borenstein NS, Levine JM, Volpe JJ, Kinney HC. Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury. J Neurosci. 2001;21:1302–12.

    PubMed  CAS  Google Scholar 

  6. Back SA, Han BH, Luo NL, Chricton CA, Xanthoudakis S, Tam J, Arvin KL, Holtzman DM. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia. J Neurosci. 2002;22:455–63.

    PubMed  CAS  Google Scholar 

  7. Craig A, Ling Luo N, Beardsley DJ, Wingate-Pearse N, Walker DW, Hohimer AR, Back SA. Quantitative analysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human. Exp Neurol. 2003;181:231–40.

    Article  PubMed  Google Scholar 

  8. Mizuno K, Hida H, Masuda T, Nishino H, Togari H. Pretreatment with low doses of erythropoietin ameliorates brain damage in periventricular leukomalacia by targeting late oligodendrocyte progenitors: a rat model. Neonatology. 2008;94:255–66.

    Article  PubMed  CAS  Google Scholar 

  9. Titomanlio L, Kavelaars A, Dalous J, Mani S, El Ghouzzi V, Heijnen C, Baud O, Gressens P. Stem cell therapy for neonatal brain injury: perspectives and challenges. Ann Neurol. 2011;70:698–712.

    Article  PubMed  Google Scholar 

  10. Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007;448:313–7.

    Article  PubMed  CAS  Google Scholar 

  11. Hida H, Takeda M, Soliven B. Ceramide inhibites inward rectifying K+ current via Ras- and raf-1-dependent pathway in cultured oligodendrocytes. J Neurosci. 1998;18(21):8712–9.

    PubMed  CAS  Google Scholar 

  12. Gallo V, Zhou JM, McBain CJ, Wright P, Knutson PL, Armstrong RC. Oligodendrocyte progenitor cell proliferation and lineage progression are regulated by glutamate receptor-mediated K+ channel block. J Neurosci. 1996;16:2659–70.

    PubMed  CAS  Google Scholar 

  13. Knutson P, Ghiani CA, Zhou JM, Gallo V, McBain CJ. K+ channel expression and cell proliferation are regulated by intracellular sodium and membrane depolarization in oligodendrocyte progenitor cells. J Neurosci. 1997;17:2669–82.

    PubMed  CAS  Google Scholar 

  14. Chittajallu R, Chen Y, Wang H, Yuan X, Ghiani CA, Heckman T, McBain CJ, Gallo V. Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle. Proc Natl Acad Sci USA. 2002;99:2350–5.

    Article  PubMed  CAS  Google Scholar 

  15. Tiwari-Woodruff S, Beltran-Parrazal L, Charles A, Keck T, Vu T, Bronstein J. K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte development. Am J Physiol Cell Physiol. 2006;291:687–98.

    Article  Google Scholar 

  16. Barres BA, Koroshetz WJ, Swartz KJ, Chun LL, Corey DP. Ion channel expression by white matter glia: the O-2A glial progenitor cell. Neuron. 1990;4:507–24.

    Article  PubMed  CAS  Google Scholar 

  17. Attali B, Wang N, Kolot A, Sobko A, Cherepanov V, Soliven B. Characterization of delayed rectifier Kv channels in oligodendrocytes and progenitor cells. J Neurosci. 1997;17:8234–45.

    PubMed  CAS  Google Scholar 

  18. Keller G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev. 2005;19:1129–55.

    Article  PubMed  CAS  Google Scholar 

  19. Wiles MV, Johansson BM. Embryonic stem cell development in a chemically defined medium. Exp Cell Res. 1999;247:241–8.

    Article  PubMed  CAS  Google Scholar 

  20. McMahon JA, Takada S, Zimmerman LB, Fan CM, Harland RM, McMahon AP. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev. 1998;12:1438–52.

    Article  PubMed  CAS  Google Scholar 

  21. Stern CD. Neural induction: old problem, new findings, yet more questions. Development. 2005;132:2007–21.

    Article  PubMed  CAS  Google Scholar 

  22. Czepiel M, Balasubramaniyan V, Schaafsma W, Stancic M, Mikkers H, Huisman C, Boddeke E, Copray S. Differentiation of induced pluripotent stem cells into functional ologodendrocytes. Glia. 2011;59:882–92.

    Article  PubMed  Google Scholar 

  23. Fragoso G, Martínez-Bermúdez AK, Liu HN, Khorchid A, Chemtob S, Mushynski WE, Almazan G. Developmental differences in HO-induced oligodendrocyte cell death: role of glutathione, mitogen-activated protein kinases and caspase 3. J Neurochem. 2004;90:392–404.

    Article  PubMed  CAS  Google Scholar 

  24. Fern R, Möller T. Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop. J Neurosci. 2000;20:34–42.

    PubMed  CAS  Google Scholar 

  25. Haider L, Fischer MT, Frischer JM, Bauer J, Höftberger R, Botond G, Esterbauer H, Binder CJ, Witztum JL, Lassmann H. Oxidative damage in multiple sclerosis lesion. Brain. 2011;134:1914–24.

    Article  PubMed  Google Scholar 

  26. Jelinski SE, Yager JY, Juurlink BH. Preferential injury of oligodendroblasts by a short hypoxic-ischemic insult. Brain Res. 1999;815:150–3.

    Article  PubMed  CAS  Google Scholar 

  27. Back SA, Gan X, Li Y, Rosenberg PA, Volpe JJ. Maturation-dependent vulnerability of oligodendrocytes to oxidative stress-induced death caused by glutathione depletion. J Neurosci. 1998;18:6241–53.

    PubMed  CAS  Google Scholar 

  28. Nash B, Thomson CE, Linington C, Arthur AT, McClure JD, McBride MW, Barnett SC. Functional duality of astrocytes in myelination. J Neurosci. 2011;31:13028–38.

    Article  PubMed  CAS  Google Scholar 

  29. Talbott JF, Loy DN, Liu Y, Qiu MS, Bunge MB, Rao MS, Whittemore SR. Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes. Exp Neurol. 2005;192:11–24.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Project for Realization of Regenerative Medicine of the Ministry of Education, Culture, Sports, Science & Technology, and a Grant-in-Aid for Scientific Research on priority Area (C) (No 23500395 to H.H.) and young Area (B) (No 23700471 to S.M.) from the Japan Society for the Promotion of Science (JSPS).

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Sachiyo Misumi, Ruriko Nishigaki, Yoshitomo Ueda, Yoko Watanabe, Yuko Shimizu, Akimasa Ishida, ChaGyun Jung & Hideki Hida

Authors
  1. Sachiyo Misumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruriko Nishigaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshitomo Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoko Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuko Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akimasa Ishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. ChaGyun Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hideki Hida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideki Hida.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Misumi, S., Nishigaki, R., Ueda, Y. et al. Differentiation of Oligodendrocytes from Mouse Induced Pluripotent Stem Cells Without Serum. Transl. Stroke Res. 4, 149–157 (2013). https://doi.org/10.1007/s12975-012-0250-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12975-012-0250-1

Keywords

Search

Navigation