Alginate-gelatin hydrogel-encapsulated Wharton’s Jelly-Derived mesenchymal stem cells improve ovarian morphology and reduce inflammation in a rat model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in young women, often leading to menstrual dysfunction and infertility. Recent advances suggest that mesenchymal stem cells (MSCs), particularly those derived from human Wharton’s jelly, may offer regenerative and immunomodulatory benefits for restoring ovarian function. This study aimed to evaluate the therapeutic effects of human Wharton’s jelly–derived mesenchymal stem cells (hWJMSCs) encapsulated to alginate-gelatin hydrogel in an experimentally induced model of PCOS. PCOS was induced in adult female Wistar rats ( n = 5 per group) by a single intramuscular injection of estradiol valerate. Forty-five days later, animals in the treatment groups received intraovarian subcapsular injection of either alginate-gelatin hydrogel (hydrogel group) or hWJMSCs encapsulated in alginate-gelatin hydrogel (hWJMSCs+hydrogel group). One month after transplantation, ovarian tissues were evaluated for histopathological changes, follicular development, corpus luteum formation, tissue levels of inflammatory cytokines (IL-6 and TNF-α), and apoptotic activity using TUNEL assay. hWJMSCs therapy significantly improved ovarian morphology, demonstrated by increased numbers of growing follicles and the reappearance of corpus luteum. Treatment markedly reduced cystic follicles and restored structural integrity of the ovarian tissue. A significant decline in pro‑inflammatory cytokines (IL‑6 and TNF‑α) was observed (IL‑6: P = 0.00012; TNF‑α: P = 0.00044), alongside a significant reduction in apoptotic cell numbers ( P = 0.0020). In contrast, the hydrogel group exhibited only marginal, non‑significant changes in these parameters relative to the hWJMSCs+hydrogel group, confirming that the hydrogel carrier itself lacked intrinsic therapeutic or synergistic effects. These findings indicate that encapsulated hWJMSCs effectively modulated the inflammatory microenvironment and supported follicular recovery in PCOS‑induced ovaries. In a rat model of PCOS, encapsulated hWJMSCs improved ovarian morphology, reduced local inflammation and apoptosis. These preliminary findings suggest that hWJMSCs‑based interventions may help modulate the ovarian microenvironment; however, studies with larger sample sizes and functional reproductive outcomes are needed to further evaluate their therapeutic potential.