Exosomes Derived from Adipose Mesenchymal Stem Cells Restore Functional Endometrium in a Rat Model of Intrauterine Adhesions.

Abstract

Intrauterine adhesion (IUA) caused by endometrial injury is one of the important causes of infertility in women of reproductive age and requires advanced treatment strategies. Increasing evidence suggests that the therapeutic effects of mesenchymal stem cells (MSC) mainly depend on their capacity to secrete paracrine factors and are mediated by MSC-derived exosomes. This study aimed to identify exosomes derived from adipose-derived mesenchymal stem cells (ADSC-exo) and explore the therapeutic potential in IUA rat models. ADSC-exo exhibited classic cup-shaped morphology with a positive expression of Alix and CD63 and were mainly concentrated at 109.5 nm. In IUA model, treatment with ADSC-exo maintained normal uterine structure, promoted endometrial regeneration and collagen remodeling, and enhanced the expression of integrin-β3, LIF, and VEGF. An improved receptivity of the regenerated endometrium was confirmed. Our findings demonstrated that ADSC-exo promoted endometrial regeneration and fertility restoration. It suggested that topical administration of ADSC-exo in uterus could be a promising strategy for patients suffering severe intrauterine adhesions and infertility.