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The use of polyethylenimine–DNA to topically deliver hTERT to promote hair growth

Abstract

The present study investigates the efficacy of polyethylenimine (PEI)–DNA complex that expressed human telomerase reverse transcriptase (hTERT) to transfect hair follicle stem cells and produce sufficient hTERT to stimulate hair growth. Transfection with pLC–hTERT–DNA–PEI complex (D+P group) in vitro induced expression of proliferating cell nuclear antigen in 35.8% of the purified stem cell population, suggesting enhanced cell proliferation. In vivo transfection efficiency of rat dorsal skin was determined by staining for β-gal activity. Cells positive for β-gal were located in the bulge region and dermal sheath of hair follicles. The follicles in the hTERT-transfected region entered anagenon day 15 after transfection, whereas non-transfected (Neg) controls remained in telogen. The similar effect was observed in 50-day-old rat dorsal skin. D+P group displayed a specific expression of hTERT and sufficient to initiate a transition to the anagen phase and promote new hair synthesis 18 days after the transfection. hTERT promoted follicle neogenesis following wounding. In all, 60 days after wounding, tissues of the D+P group showed more newly regenerating hair follicles (83±52 regenerated follicles per rat) in contrast to control group tissues (15±15 regenerated follicles per rat). These studies provide a potential approach for gene therapy of skin disease.

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References

  1. Jones PH, Watt FM . Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 1993; 73: 713–724.

    Article  CAS  Google Scholar 

  2. Tani H, Morris RJ, Kaur P . Enrichment for murine keratinocyte stem cells based on cell surface phenotype. Proc Natl Acad Sci USA 2000; 97: 10960–10965.

    Article  CAS  Google Scholar 

  3. Hwang J, Mehrani T, Millar SE, Morasso MI . Dlx3 is a crucial regulator of hair follicle differentiation and cycling. Development 2008; 135: 3149–3159.

    Article  CAS  Google Scholar 

  4. Ito M, Yang Z, Andl T, Cui C, Kim N, Millar SE et al. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 2007; 447: 316–320.

    Article  CAS  Google Scholar 

  5. Choi J, Southworth LK, Sarin KY, Venteicher AS, Ma W, Chang W et al. TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program. PLoS Genet 2008; 4: e10.

    Article  Google Scholar 

  6. Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M et al. Telomerase modulates Wnt signalling by association with target gene chromatin. Nature 2009; 460: 66–72.

    Article  CAS  Google Scholar 

  7. Sarin KY, Cheung P, Gilison D, Lee E, Tennen RI, Wang E et al. Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature 2005; 436: 1048–1052.

    Article  CAS  Google Scholar 

  8. Ohyama M, Vogel JC . Gene delivery to the hair follicle. J Investig Dermatol Symp Proc 2003; 8: 204–206.

    Article  Google Scholar 

  9. 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 

  10. 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 Therapy 2004; 11: 1033–1039.

    Article  CAS  Google Scholar 

  11. Cheng H, Zhu JL, Zeng X, Jing Y, Zhang XZ, Zhuo RX et al. Targeted gene delivery mediated by folate-polyethylenimine-block-poly(ethylene glycol) with receptor selectivity. Bioconjug Chem 2009; 20: 481–487.

    Article  CAS  Google Scholar 

  12. Shim MS, Kwon YJ . Acid-responsive linear polyethylenimine for efficient, specific, and biocompatible siRNA delivery. Bioconjug Chem 2009; 20: 488–499.

    Article  CAS  Google Scholar 

  13. Zhao QQ, Chen JL, Lv TF, He CX, Tang GP, Liang WQ et al. N/P ratio significantly influences the transfection efficiency and cytotoxicity of a polyethylenimine/chitosan/DNA complex. Biol Pharm Bull 2009; 32: 706–710.

    Article  CAS  Google Scholar 

  14. 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 

  15. Itaka K, Kataoka K . Recent development of nonviral gene delivery systems with virus-like structures and mechanisms. Eur J Pharm Biopharm 2009; 71: 475–483.

    Article  CAS  Google Scholar 

  16. Ko YT, Bhattacharya R, Bickel U . Liposome encapsulated polyethylenimine/ODN polyplexes for brain targeting. J Control Release 2009; 133: 230–237.

    Article  CAS  Google Scholar 

  17. Wong K, Sun G, Zhang X, Dai H, Liu Y, He C et al. PEI-g-chitosan, a novel gene delivery system with transfection efficiency comparable to polyethylenimine in vitro and after liver administration in vivo. Bioconjug Chem 2006; 17: 152–158.

    Article  CAS  Google Scholar 

  18. Wu Y, Fei Z, Lee LJ, Wyslouzil BE . Coaxial electrohydrodynamic spraying of plasmid DNA/polyethylenimine (PEI) polyplexes for enhanced nonviral gene delivery. Biotechnol Bioeng 2009; 105: 834–841.

    Google Scholar 

  19. Zhang L, Hu CH, Cheng SX, Zhuo RX . PEI grafted hyperbranched polymers with polyglycerol as a core for gene delivery. Colloids Surf B Biointerfaces 2010; 76: 427–433.

    Article  CAS  Google Scholar 

  20. Gao JQ, Zhao QQ, Lv TF, Shuai WP, Zhou J, Tang GP et al. Gene-carried chitosan-linked-PEI induced high gene transfection efficiency with low toxicity and significant tumor-suppressive activity. Int J Pharm 2009; 387: 286–294.

    Article  Google Scholar 

  21. Funhoff AM, van Nostrum CF, Koning GA, Schuurmans-Nieuwenbroek NM, Crommelin DJ, Hennink WE et al. Endosomal escape of polymeric gene delivery complexes is not always enhanced by polymers buffering at low pH. Biomacromolecules 2004; 5: 32–39.

    Article  CAS  Google Scholar 

  22. 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 

  23. Schlake T . Determination of hair structure and shape. Semin Cell Dev Biol 2007; 18: 267–273.

    Article  CAS  Google Scholar 

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Acknowledgements

This research work was supported by a grant from National Science Council of the Republic of China (NSC99-2218-E-002-011).

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Correspondence to P-S Lai or M-J Shieh.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on Gene Therapy website

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Jan, HM., Wei, MF., Peng, CL. et al. The use of polyethylenimine–DNA to topically deliver hTERT to promote hair growth. Gene Ther 19, 86–93 (2012). https://doi.org/10.1038/gt.2011.62

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