Comparative evaluation of the therapeutic efficacy between human amniotic epithelial cells and human umbilical cord mesenchymal stem cells in premature ovarian insufficiency.

backgroundPremature ovarian insufficiency (POI) is a clinically challenging condition characterized by amenorrhea and infertility in women less than 40 years of age. Although both human amniotic epithelial cells (hAECs) and human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown promise in treating POI, their comparative therapeutic efficacy and mechanisms remain poorly understood.

methodshAECs and hUC-MSCs were isolated from human amniotic membrane and umbilical cords, respectively, and characterized using standard protocols. A chemotherapy-induced POI mouse model was established to evaluate follicular development, ovarian fibrosis, and fertility recovery after hAEC and hUC-MSC transplantation. Longitudinal in vivo bioluminescence imaging was used to track and compare the biodistribution and retention rates of the transplanted cells. RNA sequencing and in vitro functional assays under oxidative stress and apoptosis-induced conditions were employed to analyze the differential stress responses of hAECs and hUC-MSCs. Furthermore, cytokine arrays were utilized to profile their secretomes.

resultsIn the chemotherapy-induced POI mouse model, both hAECs and hUC-MSCs transplantation improved ovarian function, as evidenced by increased ovarian weight, restored estrous cycle, elevated follicle counts, reduced fibrosis, and enhanced fertility. In vivo imaging revealed that both cell types primarily homed to the lungs, liver, and spleen post-transplantation, with signal intensity declining over time. Quantitative analysis revealed significantly longer in vivo retention of hAECs compare to hUC-MSCs. RNA sequencing and in vitro assays confirmed the superior antioxidant capacity of hAECs under stress conditions. Cytokine profiling showed that hAEC-CM was enriched in pro-angiogenic factors, while hUC-MSC-CM contained higher levels of immunoregulatory cytokines, a functional difference further validated by in vitro experiments.

conclusionOur findings demonstrate that both hAECs and hUC-MSCs are effective in restoring ovarian function and fertility in a chemotherapy-induced POI mouse model. However, these two cell types exhibit distinct therapeutic advantages attributable to their differential metabolic kinetics and paracrine profiles. Specifically, hAECs displayed prolonged in vivo retention rates compared to hUC-MSCs, consistent with their enhanced antioxidant capabilities. In terms of secretory function, hAECs demonstrated superior pro-angiogenic activity, while hUC-MSCs exhibited stronger immunomodulatory effects. These distinct properties provide critical insights for cell-type-specific selection in developing targeted therapies for ovarian dysfunction.