低氧下骨髓间充质干细胞复合细胞外基质膜片构建3D组织工程皮肤的研究

项目名称： 低氧下骨髓间充质干细胞复合细胞外基质膜片构建3D组织工程皮肤的研究

项目编号： No.81471883

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： 祁少海

作者单位： 中山大学

项目金额： 70万元

中文摘要： 组织工程皮肤构建的难点是种子细胞和支架的选择。前期实验显示：1、低氧条件下，骨髓间充质干细胞（BM-MSCs）的增殖活性、分化潜能及分泌功能更强。BM-MSCs在包被有温度敏感型水凝胶的纳米蚀刻细胞培养板上可形成排列规则、分布均匀的膜片；2、膜片经脱细胞处理形成具一定机械强度及免疫调节功能的细胞外基质（ECM）膜片,其对复种的BM-MSCs增殖、分化及分泌功能具促进作用。因此，一张于低氧条件下制备的、无人造支架、仅由大量BM-MSCs及其ECM组成的膜片使建立组织工程器官构建新途径成为可能。课题组拟将新型细胞培养模板（刻痕深250nm、宽350nm、间距700nm）引入膜片制备，使接种其上的BM-MSCs按蚀刻痕迹规则排列并形成均质的细胞膜片，与具同样规则结构的ECM膜片结合，构建新型3D组织工程皮肤，通过体内、外实验对其进行评估、优化制备工艺，为皮肤损伤修复提供新的思路与方法。

中文关键词： 低氧；骨髓间充质干细胞；细胞外基质；组织工程皮肤

英文摘要： Human mesenchymal stem cells (BM-MSCs) are being investigated as seeding cells for tissue or organ engineering in a wide range of diseases. A scaffold-free, robust cell sheet composed by aligned BM-MSCs and their extracellular matrix (ECM) offers many interesting, promising opportunities for tissue reconstruction. Previous experiments indicate: 1. BM-MSCs cultured on nanogratings coated with temperature-responsive culture surface will form a confluent, uniform BM-MSCs sheet. Compared to normoxia (20% O2), aligned BM-MSCs cultured in hypoxia (2% O2) will maintained higher differentiation and paracrine capacity; 2. The decellularized, aligned, hypoxia conditioned ECM matrices maintained better elastic modulus and repopulated BM-MSCs will have higher viability, differentiation and paracrine capacity. As for this project, we will fabricate 3D engineered skin substitute by combining BM-MSCs sheet with its decellularized ECM matrices under hypoxia. The evaluation will be conducted in vitro and in vivo. And the relative mechanism will be further discussed.

英文关键词： hypoxia;BM-MSC;extracellular matrix;bioengineered skin