TERT/BMI1-transgenic Human Dermal Papilla Cells Enhance Murine Hair Follicle Formation in Vivo.

Background: Dermal papilla cells (DPCs) are one type of mesenchymal cells; they play a key role on hair follicle induction. Their hair inductivity and proliferation abilities are rapidly lost during the 2-dimensional culture. Cell senescence is induced by inadequate culture conditions and telomere shortening. We previously reported that overexpression of TERT coding telomerase reverse transcriptase and BMI1 coding human B-cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) avoided senescence of murine DPC and restored hair inductive activity. Objective: To evaluate the function of TERT and BMI1 in the human DPCs (hDPCs). Methods: Cultured hDPCs obtained from human scalp hair were transduced with TERT alone (hDP-T), BMI1 alone (hDP-B), both TERT and BMI1 (hDP-TB) and empty vector (hDP-E). The hair inductive activity of those cells was assessed by chamber assay in vivo. Gene expressions were analyzed by quantitative PCR (q-PCR). Results: hDP-TB proliferated more than hDP-T and hDP-B in vitro and only hDP-TB showed hair inductivity in vivo. Moreover, the expressions of VCAN, CTNNB1, LEF1, FGF7 and VEGFA in hDP-TB were elevated compared to those in hDP-E. Conclusion: Overexpression of both TERT and BMI1 extends the life span of cultured hDPCs and ameliorates their hair inducing ability on mouse hair follicles. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology. CC_BY_4.0