可降解3D微支架积木引导hPSC-CMs的兴奋收缩耦联及对左室功能的研究

With the development of bio-engineering, biomaterial and cell biology, using engineered heart tissue(EHT) to replace ischemic myocardium has become a research hotspot in recent years. At present, EHT has poor excitation contraction coupling(ECC), weak systolic function, which limits its further application. Our group intend to use micro etching technology and pre polymer adhesive technology to prepare biodegradable PGS scaffolds which have specific three-dimensional micro structure. Human pluripotent stem cell derived cardiomyocytes(hPSC-CMs) are cultured on such scaffolds which could guide cell growth and connection. We hope we could find specific three dimensional mciro structure which can promote maturation, regular alignment of hPSC-CMs and imporve myocardial intercellular excitation contraction coupling. At meantime, we will use electrical stimulation and growth factor intervention to promote the overall electrical mechanical contraction of EHT. Then the EHT will be implanted into the myocardium infarction site of mouse in vivo to evaluate its effect on left ventricular function and remodeling. This study focuses on the 3D micro structure of PGS scaffold which improve the differentiation, matuatioin and ECC of hPSC-CMs, and the effect of EHT on left ventricular remodeling in vivo.

随着生物工程、材料和细胞生物学的发展，组织工程心肌（EHT）替代梗死心肌成为近年的研究热点。但目前所构建的EHT心肌细胞间的兴奋收缩耦联差，导致整体收缩功能弱。如何利用3D支架来引导和促进细胞间的连接，对EHT的整体同步收缩至关重要。前期我们利用微刻蚀等技术，制备出双层短轴叠加的可降解聚癸二酸丙三醇酯(PGS)微支架，初步引导乳鼠心肌细胞排列。然而该支架内细胞缺乏连接，且乳鼠细胞缺乏实际应用价值。本项目拟将人多能干细胞来源心肌细胞（hPSC-CMs）种植于交叉排列的3D微支架；通过支架内交通，引导hPSC-CMs的排列和连接，从而改善细胞间兴奋收缩耦联；同时进一步应用电刺激和生长因子干预，加强细胞的整体电机械收缩；进而体内移植EHT至小鼠心梗模型，评价其对左室功能的影响并探讨其作用机制。研究发现将为构建EHT提供新的思路，推动EHT的深入研究和转化应用。

随着生物工程、材料和细胞生物学的发展，组织工程心肌（EHT）替代梗死心肌成为近年的研究热点。但目前所构建的EHT心肌细胞间的兴奋收缩耦联差，导致整体收缩功能弱。如何利用3D支架来引导和促进细胞间的连接，对EHT的整体同步收缩至关重要。前期我们利用微刻蚀等技术，制备出双层短轴叠加的可降解聚癸二酸丙三醇酯(PGS)微支架，初步引导乳鼠心肌细胞排列。然而该支架内细胞缺乏连接，且乳鼠细胞缺乏实际应用价值。本项目拟将人多能干细胞来源心肌细胞（hPSC-CMs）种植于交叉排列的3D微支架；通过支架内交通，引导hPSC-CMs的排列和连接，从而改善细胞间兴奋收缩耦联；同时进一步应用电刺激和生长因子干预，加强细胞的整体电机械收缩；进而体内移植EHT至小鼠心梗模型，评价其对左室功能的影响并探讨其作用机制。研究发现将为构建EHT提供新的思路，推动EHT的深入研究和转化应用。