Liao Peilin, Xie Jinghe, Wang Jue, Lin Jiamin, Zhang Xueyan, Qin Changlu, Wang Hongyan, Duan Yuyou, Bao Huiqiong
Laboratory of Stem Cells and Translational Medicine, Institute for Life Science, School of Medicine, South China University of Technology, Guangzhou, 510006, China.
Laboratory of Stem Cells and Translational Medicine, Institute for Clinical Medicine, Second Affiliated Hospital, School of Medicine, South China University of Technology, No. 10 Huanyu Erlu, Guangzhou, 510006, China.
J Mater Chem B. 2025 Jul 16;13(28):8496-8509. doi: 10.1039/d5tb00902b.
An intact endometrium is critical for zygote implantation and embryonic development, and the recurrence rate after transcervical resection of adhesion surgery is high in patients with endometrial injury. Therefore, there is an urgent need to develop more efficient and stable treatment to solve this problem. In the present study, firstly we used gelatin as a substrate and glutamine transferase as a cross-linking agent to fabricate enzyme cross-linked gelatin hydrogels which have a microporous structure, then implanted human menstrual blood-derived mesenchymal stem cells (MenSCs) in the form of single cells or cell spheres (MenSC/Gel) into enzyme-linked hydrogels. Afterwards cell-hydrogel complexes were transplanted into the injured uterus of rats for the treatment. The results showed that MenSC/Gel could maintain the uterine cavity structure, significantly increase the intimal thickness and the number of endometrial glands, reduce scar formation and promote angiogenesis, leading to an increase in the probability of pregnancy in rats to 91.67%. RNA-seq transcriptome analysis further revealed that the treatment with MenSC/Gel induced immune response-related pathways and estrogen release-related pathways, and significantly increased the expression of Orosomucoid 1 (ORM1) that inhibits fibrosis, and reduced the expressions of H19 and Heme Oxygenase 1 (HOMX1) which promote fibrosis. In conclusion, we successfully developed and used enzyme cross-linked gelatin hydrogels to deliver human MenSCs to repair endometrial injury, and in particular, the use of cell spheres could further improve the repair effect. Therefore, our results represent a significant step towards providing a new technical solution in the clinical treatment of patients with endometrial injury.
