Fibroblasts can be directly reprogrammed into cardiomyocytes, endothelial cells or smooth muscle cells. Here we report the reprogramming of mouse tail-tip fibroblasts simultaneously into cells resembling these three cell types using the microRNA mimic miR-208b-3p, ascorbic acid and bone morphogenetic protein 4, as well as the formation of tissue-like structures formed by the directly reprogrammed cells. Implantation of the formed cardiovascular tissue into the infarcted hearts of mice led to the migration of reprogrammed cells to the injured tissue, reducing regional cardiac strain and improving cardiac function. The migrated endothelial cells and smooth muscle cells contributed to vessel formation, and the migrated cardiomyocytes, which initially displayed immature characteristics, became mature over time and formed gap junctions with host cardiomyocytes. Direct reprogramming of somatic cells to make cardiac tissue may aid the development of applications in cell therapy, disease modelling and drug discovery for cardiovascular diseases.

成纤维细胞可以直接重编程为心肌细胞、内皮细胞或平滑肌细胞。在这里，我们报告了使用 microRNA 模拟物 miR-208b-3p、抗坏血酸和骨形态发生蛋白 4 将小鼠尾尖成纤维细胞同时重编程为类似于这三种细胞类型的细胞，以及由直接重编程细胞。将形成的心血管组织植入小鼠梗塞心脏中，导致重新编程的细胞迁移到受损组织，减少局部心脏应变并改善心脏功能。迁移的内皮细胞和平滑肌细胞有助于血管形成，迁移的心肌细胞最初表现出不成熟的特征，随着时间的推移变得成熟并与宿主心肌细胞形成间隙连接。直接重新编程体细胞来制造心脏组织可能有助于开发心血管疾病的细胞治疗、疾病建模和药物发现中的应用。