Repair after damage is essential for tissue homeostasis. Postmenstrual endometrial repair is a cyclical manifestation of rapid, scar-free, tissue repair taking ∼3–5 d. Skin repair after wounding is slower (∼2 wk). In the case of chronic wounds, it takes months to 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 postmenstrual 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: migration inhibitory factor, neutrophil gelatinase–associated lipocalin, follistatin like-1, chemokine ligand-20, and secretory leukocyte protease inhibitor were selected for further investigation. Functionally, they promote repair of endometrial and keratinocyte wounds by promoting migration. Translation of these and other MF factors into a migration-inducing treatment paradigm could provide novel treatments for tissue repair.
NHHRC; Project Grant 1047756; NHMRC Senior Principal Research Fellowship 1002028; Victorian Government Infrastructure Support Program of the Hudson Institute.
The authors thank the women who volunteered for this study, and the patients who donated tissues; Rebecca D’Sylva, Patrick Martin, Samuel Hawthorn, and Laura Knott (all from Hudson Institute of Medical Research) for technical assistance; and Dr. Eugene Kapp (Walter and Eliza Hall Institute) for providing the Ludwig NR protein database. This study was funded by National Health Medical Research Council of Australia (NHHRC; Project Grant 1047756), a Contributing to Australian Scholarship and Science (CASS) grant, and the Tissue Repair and Regeneration Program and the Faculty of Health at Queensland University of Technology (to J.M.); National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship 1002028 (to L.A.S.); and the Victorian Government Infrastructure Support Program of the Hudson Institute, received from the Operational Infrastructure Research Support (OIRS) fund. The authors declare no conflicts of interest.