Despite the high complete response rate of fertility-sparing treatment in early-stage endometrial cancer (EC), the low pregnancy rate is a clinical challenge. Whether endometrium-derived mesenchymal stem cells (eMSCs) can repair damaged endometrium after EC reversal remains unclear. This study explored the potential therapeutic effects of eMSCs with suitable scaffold materials on endometrial damage caused by EC. Here, appropriate engineering scaffold materials were compared to identify the most suitable materials to carry eMSCs. Then, safety and efficacy evaluations of eMSCs with a suitable hyaluronic acid hydrogel (eMSCs/HA-GEL) were investigated in in vivo experiments with subcutaneous xenotransplantation in Balb/C nude mice and a model of endometrial mechanical injury in rats. HA-GEL has minimal cytotoxicity to eMSCs compared to other materials. Then, in vitro experiments demonstrate that eMSCs/HA-GEL enhance the inhibitory effects of progestins on EC cell biological behaviors. eMSCs/HA-GEL significantly inhibit EC cell growth and have no potential safety hazards of spontaneous tumorigenesis in Balb/C nude mouse subcutaneous xenotransplantation assays. eMSCs/HA-GEL intrauterine transplantation effectively increases endometrial thickness and glandular number, improves endometrial blood supply, reduces fibrotic areas, and improves pregnancy rates in a rat endometrial mechanical injury model. GFP-eMSCs/HA-GEL intrauterine transplantation in rats shows more GFP-eMSCs in the endometrium than GFP-eMSCs transplantation alone, and no tumor formation or suspicious cell nodules are found in the liver, kidney, or lung tissues. Our results reveal the safety and efficacy of eMSCs/HA-GEL in animal models and provide preliminary evidence for the use of eMSCs/HA-GEL as a treatment for EC-related endometrial damage.

尽管早期子宫内膜癌（EC）保留生育能力治疗的完全缓解率很高，但妊娠率低是一个临床挑战。子宫内膜来源的间充质干细胞（eMSC）是否能够修复 EC 逆转后受损的子宫内膜仍不清楚。本研究探讨了eMSCs与合适支架材料对EC引起的子宫内膜损伤的潜在治疗作用。在这里，对合适的工程支架材料进行了比较，以确定最适合携带 eMSC 的材料。然后，在Balb/C裸鼠皮下异种移植和大鼠子宫内膜机械损伤模型的体内实验中，研究了eMSCs与合适的透明质酸水凝胶（eMSCs/HA-GEL）的安全性和有效性评估。与其他材料相比，HA-GEL 对 eMSC 的细胞毒性最小。然后，体外实验证明eMSCs/HA-GEL增强了孕激素对EC细胞生物学行为的抑制作用。eMSCs/HA-GEL显着抑制EC细胞生长，并且在Balb/C裸鼠皮下异种移植试验中不存在自发肿瘤发生的潜在安全隐患。在大鼠子宫内膜机械损伤模型中，eMSCs/HA-GEL宫内移植有效增加子宫内膜厚度和腺体数量，改善子宫内膜血供，减少纤维化区域，提高妊娠率。大鼠宫内移植GFP-eMSCs/HA-GEL显示，子宫内膜中的GFP-eMSCs比单独移植的GFP-eMSCs更多，并且在肝、肾或肺组织中未发现肿瘤形成或可疑细胞结节。我们的结果揭示了 eMSCs/HA-GEL 在动物模型中的安全性和有效性，并为使用 eMSCs/HA-GEL 治疗 EC 相关子宫内膜损伤提供了初步证据。