Cellular Senescence in the Context of Inducing Hair Regrowth
One of the classes of potential regenerative medicine for hair regrowth is the transplantation of cells that will provoke skin into forming new hair follicles. Dermal papilla cells are one population that might be considered in this context. Here, researchers discuss the challenge of cellular senescence in cell therapy, as it applies to dermal papilla cells and the goal of hair growth. Cultured cells will become senescent at some pace; senescent cells when transplanted may be anything from useless to actively harmful, and variation in the proportion of cultured cells that become senescent under a given protocol may be a major issue for present stem cell therapies, accounting for a wide variation in outcomes from patient to patient and clinic to clinic.
Senescent cells secrete a senescence-associated secretory phenotype (SASP), which can induce senescence in neighboring cells. Human dermal papilla (DP) cells lose their original hair inductive properties when expanded in vitro, and rapidly accumulate senescent cells in culture. Protein and RNA-seq analysis revealed an accumulation of DP-specific SASP factors including IL-6, IL-8, MCP-1, and TIMP-2. We found that combined senolytic treatment of dasatinib and quercetin depleted senescent cells, and reversed SASP accumulation and SASP-mediated repressive interactions in human DP culture, resulting in an increased Wnt-active cell population.
In hair reconstitution assays, senolytic-depleted DP cells exhibited restored hair inductive properties by regenerating de novo hair follicles (HFs) compared to untreated DP cells. In 3D skin constructs, senolytic-depleted DP cells enhanced inductive potential and hair lineage specific differentiation of keratinocytes. These data revealed that senolytic treatment of cultured human DP cells markedly increased their inductive potency in HF regeneration, providing a new rationale for clinical applications of senolytic treatment in combination with cell-based therapies.