Paracrine effect of human stem cell-derived progenitor cells on remodeling of the vagina.

Pelvic organ prolapse (POP) due to weak support tissues is a common, debilitating condition typically treated with surgery. However, surgery is suboptimal due to associated risks and high prolapse recurrence rates. Therefore, there is a need for non-surgical therapies to restore supportive tissues, such as the vagina, following surgical intervention. In this study, we used patient induced pluripotent stem cells as a source to generate patient-specific progenitors of smooth muscle cells (pSMCs) and collected proteins secreted by these progenitor cells to examine their effects on the recipient tissues. Proteomic analysis of the conditioned media from pSMCs (pSMC-CM), which contain the secreted proteins, revealed proteins involved in extracellular matrix (ECM) remodeling. We assessed the effect of pSMC-CM on the recipient tissues using vaginal fibroblasts cultured from patients with prolapse and in a rat model of surgically injured vagina. pSMC-CM increased ECM protein expression in human vaginal fibroblasts and enhanced vaginal cell contractile function and ECM protein deposition in the surgically injured rat vagina. These findings suggest that pSMC-CM may promote vaginal contractile function and tissue extracellular matrix remodeling following surgical intervention.