Menstrual fluid factors facilitate tissue repair: Identification and functional action in endometrial and skin repair

Repair after damage is essential for tissue homeostasis. Post-menstrual repair of the uterine endometrium is a unique cyclical manifestation of rapid, scar-free, tissue repair taking ~3-5 days. Skin repair post-wounding is slower (~2 weeks) and, in the case of chronic wounds, takes months/years to restore integrity. Herein, the unique ‘rapid-repair’ endometrial environment is translated to the ‘slower-repair’ skin environment. Menstrual fluid (MF), the milieu of post-menstrual endometrial repair, facilitates healing of endometrial and keratinocyte ‘wounds’ in vitro, promoting cellular adhesion and migration, stimulates keratinocyte migration in an ex vivo human skin-reconstruct model and promotes re-epithelialization in an in vivo porcine wound model. Proteomic analysis of MF identified a large number of proteins; several proteins were selected for further investigation, with the endometrium demonstrated as the source of these factors. Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration, differing significantly from currently available wound-repair treatments, which mainly promote proliferation. Development of these and other menstrual fluid factors into a ‘migration-inducing’ treatment paradigm will provide novel therapies for tissue repair.