摘要
Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions(IUAs).Evidence shows that apoptosis occurs in a majority of grafted stem cells,and apoptotic bodies(ABs)play a critical role in compensatory tissue regeneration.However,the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail.Here,a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid(HA)hydrogel to achieve endometrial regeneration and fertility restoration.Specifically,we found that the ABs could induce macrophage immunomodulation,cell proliferation,and angiogenesis in vitro.The HA hydrogel promoted the retention of ABs and facilitated their continuous release.In a murine model of acute endometrial damage and a rat model of IUAs,in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration,resulting in the fertility restoration.Consequently,ABs show good potential as therapeutic vesicles,and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.
基金
the funding support by the National Key Research Program of China(2018YFC1004800)
the International(Regional)Cooperation and Exchange Program of China(82061160494)
the National Natural Science Foundation of China(51873184)
the Fundamental Research Funds for the Central Universities(2021FZZX005-16).
