项目名称： 新型生物衍生骨骼肌再生支架的免疫原性、修复机制和生物安全性研究

项目编号： No.81471859

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 胡志前

作者单位： 中国人民解放军第二军医大学

项目金额： 72万元

中文摘要： 再生医学技术实现骨骼肌的功能性修复是肌肉缺损治疗的研究趋势，美军方利用非组织特异性细胞外基质支架材料已实现肌组织诱导再生并临床应用。这方面课题组前期制备出新型的骨骼肌组织特异性再生支架- - 骨骼肌全器官脱细胞基质（SMWOACM），并证实其脱细胞彻底，具有平行排列的基底膜管、功能性血管网络、肌肉-肌腱接头等三维超微结构和生长因子、糖胺聚糖等生物活性成分，体外较非组织特异性细胞外基质更好的促进肌源性干细胞的增殖、迁移和分化。本课题拟明确SMWOACM对宿主免疫系统的影响，对修复区局部和全身肌源性干细胞的短期、长期效应，以及联合趋化因子对全身干细胞储备的作用并确认其代谢途径和生物安全性。研究结果将为其临床应用奠定基础。前期工作已申请发明专利、在外科顶级国际会议-美国外科年会做大会报告并被SCI期刊收录。申请者和课题合作方熟悉脱细胞基质、肌肉干细胞相关操作技术，研究目标均能实现。

中文关键词： 骨骼肌缺损；组织再生；支架材料；全器官脱细胞基质；修复机制

英文摘要： The use of regenerative medicine technology to achieve functional repair of skeletal muscle is the reaearch trend in muscle defect treatment.Currently, the U.S. Army is using the non-tissue-specific extracellular matrix scaffolds to achieve muscle induced regeneration and applying this technology to the clinical. In this aspect, our research group has developed a new type of skeletal muscle tissue-specific scaffolds- - skeletal muscle whole organ skeletal muscle acellular matrix(SMWOACM) previously, and confirmed it ofthorough decellularization, together with the complex three-dimensional microstructure of hierarchical and parallel arrayed basal lamina, muscle-tendinous connection, internal capillary network, and the bioactive contents including growth factors, glycosaminoglycans, and basement membrane structural proteins.The in vitro evaluation also confirmed SMWOACM promote muscle-derived stem cells migration, proliferation and differentiation better compared to non-tissue-specific extracellular matrix.In this project,we will make it clear the impact of SMWOACM on the host immune system, the short- and long-term effect on the local and systemic muscle-derived stem cells,the inflence on stem cell reservoir in the body when combined with chemokines, as well as the metabolic pathways and biological safety of SMWOACM. The findings will lay the foundation for the clinical application of SMWOACM and help to improve the technology. Preliminary work has been announced in the top international surgical congress-American College of Surgeons Clinical Congress and accepted by SCI journals.The applicant and participants grasp the related techniques associated with acellular matrix and muscle stem cells, which will make the research objective can definitely be achieved.

英文关键词： Muscle defect;Tissue regeneration;Scaffold;Whole organ acellular matrix;Repair mechanism