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Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex

Abstract

The topical delivery of transgenes to hair follicles has potential for treating disorders of the skin and hair. Here we show that the topical administration of liposome-DNA mixtures (lipoplex) to mouse skin and to human skin xenografts resulted in efficient in vivo transfection of hair follicle cells. Transfection depended on liposome composition, and occurred only at the onset of a new growing stage of the hair cycle. Manipulating the hair follicle cycle with depilation and retinoic acid treatment resulted in nearly 50% transfection efficiency–defined as the proportion of transfected, newly growing follicles within the xenograft. Transgenes administered in this fashion are selectively expressed in hair progenitor cells and therefore have the potential to affect the characteristics of the follicle. These findings form a foundation for the future use of topical lipoplex applications to alter hair follicle phenotype and treat diseases of the hair and skin.

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Figure 1: In vitro human hair follicle transfection assay.
Figure 2: Transfection efficiency of different lipoplex combinations in human hair follicles in vitro (A) and in mouse hair follicles in vivo (B).
Figure 3: In vivo transfection of mouse hair follicles after depilation and topical application of lipoplex (10 μg, pCMV-β-gal 50 μg pFx-1).
Figure 4: Human scalp xenograft model.

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References

  1. Cotsarelis, G., Sun, T.T. & Lavker, R.M. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell 61, 1329–1337 (1990).

    Article  CAS  Google Scholar 

  2. Lyle, S. et al. The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. J. Cell Sci. 111, 3179–3188 (1998).

    CAS  PubMed  Google Scholar 

  3. Argyris, T. Kinetics of epidermal production during epidermal regeneration following abrasion in mice. Am. J. Pathol. 83, 329–340 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Paus, R. & Cotsarelis, G. The biology of hair follicles. N. Engl. J. Med. 341, 491–497 (1999).

    Article  CAS  Google Scholar 

  5. Van Scott, E. & Ekel, T. Geometric relationships between the matrix of the hair bulb and its dermal papilla in normal and alopecia scalp. J. Invest. Dermatol. 41, 269–273 (1958).

    Google Scholar 

  6. Slominski, A. & Paus, R. Melanogenesis is coupled to murine anagen: toward new concepts for the role of melanocytes and the regulation of melanogenesis in hair growth. J. Invest. Dermatol. 101, 90S–97S (1993).

    Article  CAS  Google Scholar 

  7. Li, L. & Hoffman, R.M. The feasibility of targeted selective gene therapy of the hair follicle. Nat. Med. 1, 705–706 (1995).

    Article  Google Scholar 

  8. Cotsarelis, G. The hair follicle: dying for attention. Am. J. Pathol. 151, 1505–1509 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Felgner, P.L. et al. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. USA 84, 7413–7417 (1987).

    Article  CAS  Google Scholar 

  10. Nicolau, C. & Sene, C. Liposome-mediated DNA transfer in eukaryotic cells: dependence of the transfer efficiency on the type of liposome used, and the host cell stage. Biochem. Biophys. Acta 721, 185–190 (1982).

    Article  CAS  Google Scholar 

  11. Wilson, C. et al. Cells within the bulge region of mouse hair follicle transiently proliferate during early anagen: heterogeneity and functional differences of various hair cycles. Differentiation 55, 127–136 (1994).

    Article  CAS  Google Scholar 

  12. Chase, H. Growth of the hair. Physiol. Rev. 34, 113–126 (1954).

    Article  CAS  Google Scholar 

  13. Paus, R., Stenn, R. & Link, R. Telogen skin contains an inhibitor of hair growth. Br. J. Dermatol. 122, 777–784 (1990).

    Article  CAS  Google Scholar 

  14. Alexander, M.Y. & Akhurst, R.J. Liposome-mediated gene transfer and expression via the skin. Hum. Mol. Gen. 4, 2279–2285 (1995).

    Article  CAS  Google Scholar 

  15. Yu, W.H. et al. Topical gene delivery to murine skin. J. Invest. Dermatol. 112, 370–375 (1999).

    Article  CAS  Google Scholar 

  16. Sato, N., Leopold, P.L. & Crystal, R.G. Induction of the hair growth phase in postnatal mice by localized transient expression of Sonic hedgehog. J. Clin. Invest. 104, 855–864 (1999).

    Article  CAS  Google Scholar 

  17. Egilmez, N.K., Iwanuma, Y. & Bankert, R.B. Evaluation and optimization of different cationic liposome formulations for in vivo gene transfer. Biochem. Biophys. Res. Commun. 221, 169–173 (1996).

    Article  CAS  Google Scholar 

  18. Sorgi, F.L., Bhattacharya, S. & Huang, L. Protamine sulfate enhances lipid-mediated gene transfer. Gene Ther. 4, 961–968 (1997).

    Article  CAS  Google Scholar 

  19. Shi, Z., Curiel, D.T. & Tang, D-c. DNA-based non-invasive vaccination onto the skin. Vaccine 17, 2136–2141 (1999).

    Article  CAS  Google Scholar 

  20. Fan, H., Lin, Q., Morrissey, G.R. & Khavari, P.A. Immunization via hair follicles by topical application of naked DNA to normal skin. Nat. Biotechnol. 17, 870–872 (1999).

    Article  CAS  Google Scholar 

  21. Gilhar, A., Ullmann, Y., Berkutzki, T., Assy, B. & Kalish, R.S. Autoimmune hair loss (alopecia areata) transferred by T lymphocytes to human scalp explants on SCID mice. J. Clin. Invest. 101, 62–67 (1998).

    Article  CAS  Google Scholar 

  22. Wrone-Smith, T. & Nickoloff, B.J. Dermal injection of immunocytes induces psoriasis. J. Clin. Invest. 98, 1878–1887 (1996).

    Article  CAS  Google Scholar 

  23. Safavi, K.H., Muller, S.A., Suman, V.J., Moshell, A.N. & Melton, L.J. Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin. Proc. 70, 628–633 (1995).

    Article  CAS  Google Scholar 

  24. Van Scott, E.J. Morphologic changes in pilosebaceous units and anagen hairs in alopecia areata. J. Invest. Dermatol. 31, 35–43 (1958).

    Article  CAS  Google Scholar 

  25. Headington, J.T. & Novak, E. Clinical and histologic studies of male pattern baldness treated with topical minoxidil. Curr. Ther. Res. 36, 1098–1106 (1984).

    Google Scholar 

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Acknowledgements

We thank Dr. Leaf Huang for valuable discussions and Ms. Dorothy Campbell for excellent technical assistance. This work was supported by grants from the National Alopecia Areata Foundation.

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Correspondence to George Cotsarelis.

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Domashenko, A., Gupta, S. & Cotsarelis, G. Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex. Nat Biotechnol 18, 420–423 (2000). https://doi.org/10.1038/74480

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