原位诱导骨膜生发层祖细胞增殖结合组织工程支架在软骨损伤修复中的作用及相关机制

结题报告

项目介绍

AI项目解读

基本信息

批准号：
81672153
项目类别：
面上项目
资助金额：
59.0万
负责人：
郭秦炜
依托单位：
北京大学
学科分类：
H0604.骨、关节、软组织损伤与修复
结题年份：
2020
批准年份：
2016
项目状态：
已结题
起止时间：
2017-01-01 至2020-12-31

项目参与者：
梅宇；谢兴；张辛；代岭辉；陈临新；黄洪杰；史尉利；张跃钟；
关键词：
微小核糖核酸组织工程支架骨膜生发层祖细胞软骨转化生长因子

项目摘要

This study employs subperiosteal injection of TGF-β (transforming growth factor- beta) to promote proliferation of PDPCs (periosteal-derived progenitor cells) in cambi-um layer of the periosteum in situ, thus to improve its capacity of chondrogenesis. PDPCs pretreated by TGF-β are combined with solid-supported chitosan hydrogel bi-phasic scaffold, and transplanted into knee joints to induce differentiation of hyaline cartilage to repair cartilage defects. This technique harvests in situ pretreated PDPCs , and there is no need of in vitro culture of stem cells, progenitor cells or chondrocytes. Matrix production and chondrogenic differentiation of PDPCs in the hybrid scaffold are superior to its precursors. Its easy preparation,favourable biophysical properties and chondrogenic capacity indicated that this method could be attractive for cartilage tissue engineering.In conclusion, this technique of cartilage repair is simple to perform and effective in promoting cartilage regeneration. This study will be the first that used TGF-β to improve the proliferation in situ, and transplants the pre-treated PDPCs combined with biphasic scaffold to repair cartilage defects. This method could inspire new approaches for cartilage repair using stem cells, and provide them with scientific basis. This simple and effective approach could be further studied and is promising to be applied in the clinical, which will surely bring enormous benefits.

关节软骨损伤的治疗研究是医学研究的难点，本项目在已有基础上研究原位诱导骨膜祖细胞结合组织工程支架修复软骨损伤的效果及相关机制。通过骨膜下注射TGF-β促进骨膜祖细胞原位增殖，同时研究miRNA-101对骨膜祖细胞成软骨分化的调控机制；最后将原位增殖的骨膜匀浆与含缓释TGF-β微球的壳聚糖水凝胶-脱钙骨双相功能性支架结合，以期提高软骨损伤修复的效果。创新点有：1）原位诱导骨膜祖细胞增殖，通过体内原位标记明确增殖细胞类型；2）研究miRNA-101在骨膜祖细胞向软骨细胞分化的调控机制；3）构建高效的具有缓释生长因子能力的双相功能支架；4）提出保留骨膜祖细胞生长微环境结合组织工程支架修复软骨损伤的新思路。课题将在这一领域首次研究TGF-β促骨膜细胞增殖的类型以及骨膜祖细胞成软骨分化中miRNA-101的调控机制，同时结合双相功能支架修复动物关节软骨损伤的效果，为今后治疗关节软骨损伤提供新的思。

结项摘要

关节软骨损伤的治疗研究是医学研究的难点，本项目在已有基础上研究原位诱导骨膜祖细胞结合组织工程支架修复软骨损伤的效果及相关机制。通过体外分离骨膜干（祖）细胞，结合缓释微球和脱钙骨—壳聚糖水凝胶支架，用于修复关节软骨缺损；再通过动物实验对比骨膜干细胞移植物和骨软骨移植物修复小型猪膝关节软骨缺损的效果，最终得出骨膜干细胞移植物对于修复关节软骨缺损的作用。本实验从体内和体外层面探究了骨膜干细胞对于关节软骨修复的作用及机制，同时结合双相功能支架修复动物关节软骨损伤的效果，为今后治疗关节软骨损伤提供新的思路。