Adult organs are maintained through a tightly regulated balance of proliferation, differentiation, and self-renewal of stem cells during normal tissue homeostasis or tissue repair. The basal layer of the interfollicular epidermis consists of rare quiescent and more prevalent actively cycling stem and progenitor cells. The proliferating basal keratinocytes are responsible for constant tissue regeneration and are characterized by increased metabolism coupled with prevention of commitment to differentiation. We have recently shown that mechanical stimulation of the epidermis can induce the release of the neuromodulator oxytocin in isolated skin samples in the absence of any central nervous system involvement. Here we investigated if increased oxytocin levels following mechanical stimulation affect the proliferation rates in the basal layer of the epidermis. We utilized a previously developed system to mechanically stimulate human skin explants in a controlled manner with an electronically driven vibrational applicator attached to a computer-controlled XYZ-stage. We exposed discarded, total thickness human skin explants, which were procured within a few hours after surgery, to mechanical stimuli (85Hz) frequencies for 70 seconds. We analyzed the proliferation rates in the basal layer of the epidermis 24 hrs later by immunostaining for the proliferation marker Ki67.
We report a significant increase in the number of basal keratinocytes with a positive signal for Ki67 after mechanical stimulation with 85Hz. Furthermore, our results indicate that the elevated basal cell proliferation is a consequence of the increased activity of the oxytocin receptor as the effects of the mechanical stimulation can be rescued by the application of an Oxytocin receptor antagonist. Mechanical stimulation of the skin can induce increased proliferation of the basal epidermal keratinocytes. These effects correlate with the elevated levels of Oxytocin and can be prevented by a blockade of Oxytocin receptor activation. The possibility to use mechanical stimulation to induce an increase in epidermal renewal, possibly through an increase in oxytocin levels (and potentially other neuromodulators), warrants further studies of the utility of mechanical stimulation as a therapeutic intervention.

ESDRLB012 - Oxytocin receptor-mediated proliferation of the basal epidermal layer in human skin explants after mechanical stimulation

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING