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Isolation of multipotent adult stem cells from the dermis of mammalian skin

Abstract

We describe here the isolation of stem cells from juvenile and adult rodent skin. These cells derive from the dermis, and clones of individual cells can proliferate and differentiate in culture to produce neurons, glia, smooth muscle cells and adipocytes. Similar precursors that produce neuron-specific proteins upon differentiation can be isolated from adult human scalp. Because these cells (termed SKPs for skin-derived precursors) generate both neural and mesodermal progeny, we propose that they represent a novel multipotent adult stem cell and suggest that skin may provide an accessible, autologous source of stem cells for transplantation.

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Figure 1: SKPs are dividing, nestin-positive cells that can differentiate into neurons.
Figure 2: SKPS can generate glial cells.
Figure 3: Production of nestin and fibronectin by SKPs.
Figure 4: SKPs can differentiate into smooth muscle cells and adipocytes.
Figure 5: Clonal analysis indicates that individual SKPs can give rise to neural and mesodermal cell types.
Figure 6: Isolation and differentiation of SKPs from human skin.

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References

  1. Reynolds, B. A. & Weiss, S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255, 1707–1710 (1992).

    Article  CAS  PubMed  Google Scholar 

  2. Gage, F. H. Mammalian neural stem cells. Science 287, 1433–1438 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. Prockop, D. J. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276, 71–74 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Weissman, I. L. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 287, 1442–1446 (2000).

    Article  CAS  PubMed  Google Scholar 

  5. Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143–147 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Tropepe, V. et al. Retinal stem cells in the adult mammalian eye. Science 287, 2032–2036 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. Jackson, K. A., Mi, T. & Goodell, M. A. Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc. Natl Acad. Sci. USA 96, 14482–14486 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gussoni, E. et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401, 390–394 (1999).

    CAS  PubMed  Google Scholar 

  9. Bjornson, C. R., Rietze, R. L., Reynolds, B. A., Magli, M. C. & Vescovi, A. L. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283, 534–537 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Galli, R. et al. Skeletal myogenic potential of human and mouse neural stem cells. Nature Neurosci. 3, 986–991 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Clarke, D. L. et al. Generalized potential of adult neural stem cells. Science 288, 1660–1663 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Ferrari, G. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279, 1528–1530.

  13. Petersen, B. E. et al. Bone marrow as a potential source of hepatic oval cells. Science 284, 1168–1170 (1999).

    Article  CAS  PubMed  Google Scholar 

  14. Mezey, E., Chandross, K. J., Harta, G., Maki, R. A. & McKercher, S. R. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290, 1779–1782 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Brazelton, T. R., Rossi, F. M. V., Keshet, G. I. & Blau, H. M. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290, 1775–1779 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. McDonald, J. W. et al. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nature Med. 5, 1410–1412 (1999).

    Article  CAS  PubMed  Google Scholar 

  17. Brustle, O. et al. Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285, 754–756 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Bjorklund, A. & Lindvall, O. Cell replacement therapies for central nervous system disorders. Nature Neurosci. 3, 537–544, 2000.

  19. Nurse, C. A., Macintyre, L. & Diamond, J. Reinnervation of the rat touch dome restores the Merkel cell population reduced after denervation. Neuroscience 13, 563–571 (1984).

    Article  CAS  PubMed  Google Scholar 

  20. Reynolds, B. A., Tetzlaff, W. & Weiss, S. A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J. Neurosci. 12, 4565–4574 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lendahl, U., Zimmerman, L. B. & McKay, R. D. CNS stem cells express a new class of intermediate filament protein. Cell 60, 585–595 (1990).

    Article  CAS  PubMed  Google Scholar 

  22. Gloster, A. et al. The Ta1 α-tubulin promoter specifies gene expression as a function of neuronal growth and regeneration in transgenic mice. J. Neurosci. 14, 7319–7330 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gloster, A., El-Bizhri, H., Bamji, S. X. & Miller, F. D. Early induction of the Tα1 α-tubulin promoter in developing neurons. J. Comp. Neurol. 405, 45–60 (1999).

    Article  CAS  PubMed  Google Scholar 

  24. Raff, M. C. Glial cell diversification in the rat optic nerve. Science 243, 1450–1455 (1989).

    Article  CAS  PubMed  Google Scholar 

  25. Morrison, S. J., White, P. M., Zock, C & Anderson, D. J. Prospective identification, isolation by flow cytometry, and in vivo self-renewal of multipotent mammalian neural crest stem cells. Cell 96, 737–749 (1999).

    Article  CAS  PubMed  Google Scholar 

  26. Azizi, S. A., Stokes, D., Augelli, B. J., DiGirolamo, G. & Prockop, D. J. Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats — similarities to astrocyte grafts. Proc. Natl Acad. Sci. USA 95, 3908–3913 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Carpenter, M. K. et al. In vitro expansion of a multipotent population of human neural progenitor cells. Exp. Neurol. 158, 265–278 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Woodbury, D., Schwarz, E. J., Prockop, D. J. & Black, I. B. Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61, 364–370 (2000).

    Article  CAS  PubMed  Google Scholar 

  29. Slack, R. S., El-Bizri, H., Wong, J., Belliveau, D. J. and Miller, F. D. A critical temporal requirement for the retinoblastoma protein family during neuronal determination. J. Cell Biol. 140, 1497–1509.

  30. Toma, J. G., El-Bizri, H., Barnabe-Heider, F., Aloyz, R. & Miller, F. D. Evidence that HLH proteins collaborate with pRb to regulate cortical neurogenesis. J. Neurosci. 20, 7648–7656 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Park, J. K., Williams, B. P., Alberta, J. A. & Stiles, C. D. Bipotent cortical progenitor cells process conflicting cues for neurons and glia in a hierarchical manner. J. Neurosci. 19, 10383–10389 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank Y. Wang-Ninio, A. Aumont and M. Fortier for their advice and assistance during the course of this project. F.D.M. is a CIHR Senior Scientist and Killam Scholar, D.R.K. a Harold Johns NCIC Scholar, and K.J.L.F. and F.B.-H. are supported by a CIHR/Neurotrauma fellowship and an NSERC studentship, respectively. This work was supported by a research contract from Aegera Therapeutics and research grants from the CIHR.

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Correspondence to Freda D. Miller.

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Toma, J., Akhavan, M., Fernandes, K. et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol 3, 778–784 (2001). https://doi.org/10.1038/ncb0901-778

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