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Hair follicle stem cell-targeted gene transfer and reconstitution system

Abstract

Gene transfer to hair follicle (HF) epithelium is an attractive approach for not only treating skin diseases, but also many systemic disorders. In this study, we attempted to develop a gene transfer system for HF epithelial stem cells to maximize the beneficial therapeutic effects. For persistent and stable transgene expression in HF stem cells, we transferred retroviral vectors encoding reporter genes into cultured HF stem cells. In addition, these cells were mixed with cultured dermal papilla cells and transplanted on to immunodeficient mice. We succeeded in reconstituting HFs and their appendages in which these cells harbored a transgene reporter. The transgene expression was observed in all skin epithelial compartments including the HF epithelium, sebaceous gland and epidermis. In addition, transgene expression was observed for at least 6 months. This HF stem cell-targeted gene transfer and reconstitution system provides reliable gene-function analysis and gene therapy.

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References

  1. Li L, Hoffman RM . The feasibility of targeted selective gene therapy of the hair follicle. Nat Med 1995; 1: 705–706.

    Article  Google Scholar 

  2. Sato N, Leopold PL, Crystal RG . Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog. J Clin Invest 1999; 104: 855–864.

    Article  CAS  Google Scholar 

  3. Domashenko A, Gupta S, Cotsarelis G . Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex. Nat Biotechnol 2000; 18: 420–423.

    Article  CAS  Google Scholar 

  4. Yang CH, Shen SC, Lee JC, Wu PC, Hsueh SF, Lu CY et al. Seeing the gene therapy: application of gene gun technique to transfect and decolour pigmented rat skin with human agouti signalling protein cDNA. Gene Ther 2004; 11: 1033–1039.

    Article  CAS  Google Scholar 

  5. Saito N, Zhao M, Li L, Baranov E, Yang M, Ohta Y et al. High efficiency genetic modification of hair follicles and growing hair shafts. Proc Natl Acad Sci USA 2002; 99: 13120–13124.

    Article  CAS  Google Scholar 

  6. Cotsarelis G, Sun TT, Lavker RM . Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 1990; 61: 1329–1337.

    Article  CAS  Google Scholar 

  7. Lavker RM, Cotsarelis G, Wei ZG, Sun TT . Stem cells of pelage, vibrissae, and eyelash follicles: the hair cycle and tumor formation. Ann NY Acad Sci 1991; 642: 214–224; discussion 224–225.

    Article  CAS  Google Scholar 

  8. Lavker RM, Miller SJ, Sun TT . Epithelial stem cells, hair follicles, and tumor formation. Recent Results Cancer Res 1993; 128: 31–43.

    Article  CAS  Google Scholar 

  9. Sun TT, Cotsarelis G, Lavker RM . Hair follicular stem cells: the bulge-activation hypothesis. J Invest Dermatol 1991; 96: 77S–78S.

    Article  CAS  Google Scholar 

  10. Kobayashi K, Rochat A, Barrandon Y . Segregation of keratinocyte colony-forming cells in the bulge of the rat vibrissa. Proc Natl Acad Sci USA 1993; 90: 7391–7395.

    Article  CAS  Google Scholar 

  11. Rochat A, Kobayashi K, Barrandon Y . Location of stem cells of human hair follicles by clonal analysis. Cell 1994; 76: 1063–1073.

    Article  CAS  Google Scholar 

  12. Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM . Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell 2000; 102: 451–461.

    Article  CAS  Google Scholar 

  13. Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y . Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell 2001; 104: 233–245.

    Article  CAS  Google Scholar 

  14. Morris RJ, Liu Y, Marles L, Yang Z, Trempus C, Li S et al. Capturing and profiling adult hair follicle stem cells. Nat Biotechnol 2004; 22: 411–417.

    Article  CAS  Google Scholar 

  15. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M et al. Defining the epithelial stem cell niche in skin. Science 2004; 303: 359–363.

    Article  CAS  Google Scholar 

  16. Blanpain C, Lowry WE, Geoghegan A, Polak L, Fuchs E . Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 2004; 118: 635–648.

    Article  CAS  Google Scholar 

  17. Ghazizadeh S, Harrington R, Taichman L . In vivo transduction of mouse epidermis with recombinant retroviral vectors: implications for cutaneous gene therapy. Gene Therapy 1999; 6: 1267–1275.

    Article  CAS  Google Scholar 

  18. Miller DG, Adam M, Miller AD . Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol 1990; 10: 4239–4242.

    Article  CAS  Google Scholar 

  19. Li L, Mignone J, Yang M, Matic M, Penman S, Enikolopov G et al. Nestin expression in hair follicle sheath progenitor cells. Proc Natl Acad Sci USA 2003; 100: 9958–9961.

    Article  CAS  Google Scholar 

  20. Amoh Y, Li L, Yang M, Moossa AR, Katsuoka K, Penman S et al. Nascent blood vessels in the skin arise from nestin-expressing hair-follicle cells. Proc Natl Acad Sci USA 2004; 101: 13291–13295.

    Article  CAS  Google Scholar 

  21. Amoh Y, Li L, Katsuoka K, Penman S, Hoffman RM . Multipotent nestin-positive, keratin-negative hair-follicle bulge stem cells can form neurons. Proc Natl Acad Sci USA 2005; 102: 5530–5534.

    Article  CAS  Google Scholar 

  22. Weinberg WC, Goodman LV, George C, Morgan DL, Ledbetter S, Yuspa SH et al. Reconstitution of hair follicle development in vivo: determination of follicle formation, hair growth, and hair quality by dermal cells. J Invest Dermatol 1993; 100: 229–236.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr James R McMillan for critical proofreading of this manuscript. This work was supported in part by Grant-in-Aid from the Ministry of Education, Science, Sports and Culture of Japan (Kiban B 16390312 to MA), the Health and Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan (H16-Research on Measures for Intractable Deseases-05 to HS) and the Ministry of Education, Science, Sports and Culture of Japan (Project for Realization of Regenerative Medicine to HS).

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Correspondence to M Akiyama.

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Supplementary Information accompanies the paper on the Gene Therapy website (http://www.nature.com/gt).

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Sugiyama-Nakagiri, Y., Akiyama, M. & Shimizu, H. Hair follicle stem cell-targeted gene transfer and reconstitution system. Gene Ther 13, 732–737 (2006). https://doi.org/10.1038/sj.gt.3302709

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