An Acellular Scaffold Facilitates Endometrial Regeneration and Fertility Restoration via Recruiting Endogenous Mesenchymal Stem Cells
An Acellular Scaffold Facilitates Endometrial Regeneration and Fertility Restoration via Recruiting Endogenous Mesenchymal Stem Cells
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无细胞支架通过招募内源性间充质干细胞促进子宫内膜再生和生育能力恢复
DOI：
10.1002/adhm.202201680
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发表时间：
2022-09-09
影响因子：
10
通讯作者：
Zhang, Songying
中科院分区：
文献类型：
--
作者：
Xin, Liaobing;Zheng, Xiaowen;Zhang, Songying
严重的子宫内粘连（IUAs），其特征是子宫内膜修复不足和纤维化，可导致不孕。以干细胞为基础的治疗，将间充质干细胞（MSCs）输送到伤口部位，在子宫内膜再生方面具有相当大的前景。然而，一些值得注意的障碍，如干性丧失、免疫原性、保留率和存活率低，限制了它们的临床应用。有证据表明，动员内源性MSCs招募的策略可以克服外源性干细胞治疗的传统局限性。本研究探索了一种名为基质衍生因子-1 α (SDF-1 α)/ e7修饰胶原支架（CES）的脱细胞生物材料。在大鼠子宫内膜急性损伤模型和大鼠IUA模型中，基于利用机体先天再生潜能的CES能够实现近乎完全的子宫内膜再生和生育恢复。在机制上，CES植入通过巨噬细胞协调策略促进内源性MSCs募集；然后，归巢的间充质干细胞发挥免疫调节和改变局部微环境的功能，以促进再生。综上所述，CES利用内源性MSCs，克服了传统细胞疗法的局限性，可以作为临床可行的无细胞治疗IUA的高疗效策略。
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-1 alpha)/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.