Senolytic Activities of TLR Agonist Stimulated Mesenchymal Stem Cell Secretome Based Cosmetic GlowSelle™ 2265705

Introduction Conditioned media of TLR stimulated mesenchymal stem cells (MSC) have been shown to induce various regenerative activities including stimulation of endogenous progenitor cells and anti-apoptotic effects in dermal progenitor cells. Numerous studies have shown senolytics possess anti-aging properties. The current study assessed effects of GlowSelle on senescent cells. Methods GlowSelle was administered dermally in a mouse model of stress induced senescence. Assessment of senescence associated cellular markers (p16, p21, SA beta-gal) was performed in GlowSelle-treated and vehicle-treated animals. Quantification of senescence associated secretory phenotype (SASP) proteins was assessed locally and systemically. Antibody blocking studies were performed to assess mechanism of senolytic activity. Results Using the photoaging model, a stress-dependent increase in expression of senescence markers was observed. GlowSelle treatment reduced senescent cells through apoptotic mechanisms. Dose dependent SASP reduction was observed locally and systemically. Blockade of HGF activity indicated a partial involvement of this cytokine in GlowSelle-mediated senolysis. Conclusion In addition to stimulation of regenerative activity, GlowSelle appears to mediate rejuvenating activity through an HGF-dependent senolytic activity.