Transient Senescence Induces Wound Healing Through SASP Factors: Therapeutic Potentials of Chick Early Amniotic Fluid (ceAF)

Abstract Background Inflammatory, proliferative and remodelling phases constitute a cutaneous wound healing program. Therapeutic applications/medication are available; however, they commonly comprise fortified preservatives that might prolong the healing process. Chick early amniotic fluids (ceAF) contain native therapeutic factors with balanced chemokines, cytokines and growth-related factors; their origins in principle dictate no existence of harmful agents that would otherwise hamper embryo development. Instead, they possess a spectrum of molecules driving expeditious mitotic divisions and possibly exerting other functions. Methods Employing both in vitro and in vivo models, we examined ceAF’s therapeutic potentials in wound healing and found intriguing involvement of transient senescence, known to be intimately intermingled with Senescence Associated Secretory Phenotypes (SASP) that function in addition to or in conjunction with ceAF to facilitate wound healing. Results In our in vitro and in vivo cutaneous wound healing models, a low dose of ceAF exhibited the best efficacies; however, higher doses attenuated the wound healing, presumably by inducing p16 expression. Conclusion Our studies link an INK4/ARF locus-mediated signalling to cutaneous wound healing, implicate the therapeutic potentials of ceAF exerting functions likely by driving transient senescence and expediting cell proliferation, and conceptualize a homeostatic and/or balanced dosage strategy in medical intervention.