A major hurdle in cardiac cell therapy is the lack of a bona fide autologous stem-cell type that can be expanded long-term and has authentic cardiovascular differentiation potential. Here we report that a proliferative cell population with robust cardiovascular differentiation potential can be generated from mouse or human fibroblasts via a combination of six small molecules. These chemically induced cardiovascular progenitor cells (ciCPCs) self-renew long-term in fully chemically defined and xeno-free conditions, with faithful preservation of the CPC phenotype and of cardiovascular differentiation capacity in vitro and in vivo. Transplantation of ciCPCs into infarcted mouse hearts improved animal survival and cardiac function up to 13 weeks post-infarction. Mechanistically, activated fibroblasts revert to a plastic state permissive to cardiogenic signals, enabling their reprogramming into ciCPCs. Expanded autologous cardiovascular cells may find uses in drug discovery, disease modelling and cardiac cell therapy.

心脏细胞治疗的一个主要障碍是缺乏真正的自体干细胞类型，这种干细胞类型可以长期扩增并具有真正的心血管分化潜力。在这里，我们报告通过六种小分子的组合，可以从小鼠或人类成纤维细胞中产生具有强大心血管分化潜力的增殖细胞群。这些化学诱导的心血管祖细胞 (ciCPC) 在完全化学定义和无异种物质的条件下长期自我更新，在体外和体内忠实地保留了 CPC 表型和心血管分化能力。将 ciCPCs 移植到梗塞小鼠心脏中可改善动物存活率和心脏功能，直至梗塞后 13 周。机械地，活化的成纤维细胞恢复到允许心源性信号的可塑性状态，使其能够重新编程为 ciCPC。扩增的自体心血管细胞可用于药物发现、疾病建模和心脏细胞治疗。