Wallace H. Coulter Department of Biomedical Engineering , Georgia Institute of Technology and Emory University School of Medicine , Atlanta , Georgia 30332 , United States.
School of Chemistry and Biochemistry, School of Chemical and Biological Engineering , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States.
ACS Appl Mater Interfaces. 2019 May 22;11(20):18242-18253. doi: 10.1021/acsami.9b04473. Epub 2019 May 7.
Congenital heart disease is the number one cause of birth defect-related death because it often leads to right ventricular heart failure (RVHF). One promising avenue to combat this RVHF is the use of cardiac patches composed of stem cells and scaffolds. Herein, we demonstrate a reparative cardiac patch by combining neonatal or child c-kit progenitor cells (CPCs) with a scaffold composed of electrospun polycaprolactone nanofibers. We examined different parameters of the patch, including the alignment, composition, and surface properties of the nanofibers, as well as the age of the CPCs. The patch based on uniaxially aligned nanofibers successfully aligned the CPCs. With the inclusion of gelatin in the nanofiber matrix and/or coating of fibronectin on the surface of the nanofibers, the metabolism of both neonatal and child CPCs was generally enhanced. The conditioned media collected from both patches based on aligned and random nanofibers could reduce the fibrotic gene expression in rat cardiac fibroblasts, following stimulation with transforming growth factor β. Furthermore, the conditioned media collected from the nanofiber-based patches could lead to the formation of tubes of human umbilical vein endothelial cells, indicating the pro-angiogenic capability of the patch. Taken together, the electrospun nanofiber-based patches are a suitable delivery vehicle for CPCs and can confer reparative benefit through anti-fibrotic and pro-angiogenic paracrine signaling.
先天性心脏病是导致与出生缺陷相关死亡的首要原因，因为它通常会导致右心室心力衰竭（RVHF）。一种有前途的治疗 RVHF 的方法是使用由干细胞和支架组成的心脏补片。在此，我们通过将新生儿或儿童 c-kit 前体细胞（CPCs）与由静电纺丝聚己内酯纳米纤维组成的支架相结合，展示了一种修复性心脏补片。我们研究了补片的不同参数，包括纳米纤维的取向、组成和表面性质，以及 CPCs 的年龄。基于单轴取向纳米纤维的补片成功地将 CPCs 定向排列。通过在纳米纤维基质中加入明胶和/或在纳米纤维表面涂覆纤连蛋白，通常可以增强新生儿和儿童 CPCs 的代谢。从基于定向和随机纳米纤维的两种补片中收集的条件培养基可以减少转化生长因子 β刺激后大鼠心肌成纤维细胞的纤维化基因表达。此外，从纳米纤维基补片中收集的条件培养基可以导致人脐静脉内皮细胞形成管，表明补片具有促血管生成能力。总之，静电纺丝纳米纤维基补片是 CPCs 的合适递送载体，并通过抗纤维化和促血管生成旁分泌信号传递修复益处。
