<p>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 secretomes from these progenitor cells to examine their paracrine effects. Proteomic analysis of the conditioned media from pSMCs (pSMC-CM), which contain the secretomes, revealed proteins involved in extracellular matrix (ECM) remodeling. We assessed the paracrine effect of pSMC-CM using vaginal fibroblasts from POP patients and in a rat model of surgically injured vagina. pSMC-CM increased ECM protein expression in human vaginal fibroblasts and enhanced vaginal 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.</p>