脱细胞基质和骨髓间充质干细胞构建组织工程阴道及其中经典Wnt信号通路调控机制研究

Successful vaginal reconstruction means important significance to the quality of life of patients with vaginal absence, and autologous tissues have been used as tissue resource. However, current employed seed cells have limited resource and may cause damage to the original tissue. Tissue engineering technology may achieve perfect reconstruction.Acellular tissue matrices have attracted much attention because of their advantages.The use of bone marrow mesenchymal stem cells (MSCs) may provide an ideal tissue source for vaginal reconstruction, which have been used to build up a variety of organization with adequate source. We have found that VECs can trigger epithelial differentiation of MSCs through a mechanism that may include activation of canonical Wnt signaling in vitro.First，we'll apply small intestinal submucosa(SIS), urinary bladder matrix (UBM)and acellular vagina matrix (AVM) to reconstruct vagina in situ,in order to select the optimal scaffold.Then transplant the MSCs(with or without VECs) into the optimal scaffold to reconstruct vagina in vivo,in order to select the optimal compound protocol and observe the role of canonical Wnt signaling in the formation of neovagina. This study aimed to look for the ideal scaffold,explore the feasibility of seeding MSCs into scaffold to reconstruct tissue-engineered vagina and clarify the mechanism of canonical Wnt signaling in the formation of vaginal reconstruction engineering for the potential bench-to-bed application in the future.

阴道重建对改善阴道缺失女性的生活质量具有重要意义。自体组织构建组织工程阴道已有报道，但其来源有限，以伤疗伤。组织工程技术有望实现完美替代。脱细胞基质材料因其优点受到广泛关注。骨髓间充质干细胞（MSCs）已用于构建多种组织，来源充足，可能为阴道重建提供理想种子细胞。课题组前期研究发现MSCs可通过与阴道上皮细胞(VECs)共培养向VECs分化，激活Wnt通路增加VECs标记表达。本研究首先应用小肠黏膜下层（SIS）、脱细胞膀胱（UBM）及脱细胞阴道（AVM）原位构建组织工程阴道，筛选最优支架；然后将MSCs联合或不联合VECs接种于最优支架上体内构建组织工程阴道，筛选最优复合方案，并探讨Wnt通路在新阴道形成中的作用。从而为组织工程阴道寻找合适支架材料，探讨MSCs与支架复合物构建组织工程阴道的可行性，阐明Wnt通路在MSCs构建的组织工程阴道中的调控机制，为组织工程阴道的临床转化奠定基础。

阴道重建对改善阴道缺失女性的生活质量具有重要意义。自体组织构建组织工程阴道已有报道，但其来源有限，以伤疗伤。组织工程技术有望实现完美替代。脱细胞基质材料因其优点受到广泛关注。骨髓间充质干细胞（MSCs）已用于构建多种组织，来源充足，可能为阴道重建提供理想种子细胞。本研究首先制备了小肠黏膜下层（SIS）、脱细胞膀胱（UBM）及脱细胞阴道（AVM），并应用其原位构建组织工程阴道，筛选最优支架为AVM；然后将MSCs接种于最优支架上体内构建组织工程阴道，筛选出其为最优复合方案，并探讨Wnt通路在新阴道形成中的作用。从而为组织工程阴道寻找合适支架材料，探讨MSCs与支架复合物构建组织工程阴道的可行性，阐明Wnt通路在MSCs构建的组织工程阴道中的调控机制，为组织工程阴道的临床转化奠定基础。