Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.
Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province. No. 3 Qingchun East Road, Jianggan District, Hangzhou, 310016, China.
Adv Healthc Mater. 2022 Nov;11(21):e2201680. doi: 10.1002/adhm.202201680. Epub 2022 Sep 9.
Severe intrauterine adhesions (IUAs), characterized by inadequate endometrial repair and fibrosis, can lead to infertility. Stem cell-based therapies, which deliver mesenchymal stem cells (MSCs) to the wound site, hold a considerable promise for endometrium regeneration. However, some notable hurdles, such as stemness loss, immunogenicity, low retention and survival rate, limit their clinical application. Evidence shows a strategy of mobilizing endogenous MSCs recruitment can overcome the traditional limitations of exogenous stem cell-based therapies. Here, an acellular biomaterial named stromal derived factor-1 alpha (SDF-1α)/E7-modified collagen scaffold (CES) is explored. CES based on harnessing the innate regenerative potential of the body enables near-complete endometrium regeneration and fertility restoration both in a rat endometrium acute damage model and a rat IUA model. Mechanistically, the CES implantation promotes endogenous MSCs recruitment via a macrophage-coordinated strategy; then the homing MSCs exert the function of immunomodulation and altered local microenvironments toward regeneration. To conclude, CES, which can harness endogenous MSCs and overcome the traditional limitations of cell-based therapies, can serve as a clinically feasible and cell-free strategy with high therapeutic efficiency for IUA treatment.
严重的宫腔粘连（IUAs）表现为子宫内膜修复不良和纤维化，可导致不孕。基于干细胞的疗法通过将间充质干细胞（MSCs）输送到创伤部位，为子宫内膜再生带来了很大的希望。然而，一些显著的障碍，如干细胞特性丧失、免疫原性、低保留率和存活率，限制了它们的临床应用。有证据表明，动员内源性 MSC 募集的策略可以克服传统外源性基于干细胞的治疗方法的局限性。在这里，研究了一种名为基质衍生因子-1α（SDF-1α）/E7 修饰胶原支架（CES）的无细胞生物材料。CES 利用机体固有的再生潜能，在大鼠子宫内膜急性损伤模型和大鼠 IUA 模型中实现了近乎完全的子宫内膜再生和生育力恢复。从机制上讲，CES 通过巨噬细胞协调策略促进内源性 MSC 的募集；然后归巢的 MSC 发挥免疫调节功能，并改变局部微环境以促进再生。总之，CES 可以利用内源性 MSC 并克服细胞治疗的传统局限性，是一种具有高治疗效率的临床可行且无细胞策略，可用于治疗 IUA。
