Li Xiao-Hong, Li Qianqian, Jiang Lin, Deng Chunyu, Liu Zaiyi, Fu Yongheng, Zhang Mengzhen, Tan Honghong, Feng Yuliang, Shan Zhixin, Wang Jianjun, Yu Xi-Yong
Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China Biochemistry and Molecular Biology Department, Wayne State University School of Medicine, Detroit, Michigan, USA.
Biochemistry and Molecular Biology Department, Wayne State University School of Medicine, Detroit, Michigan, USA.
Stem Cells Transl Med. 2015 Dec;4(12):1415-24. doi: 10.5966/sctm.2015-0136. Epub 2015 Nov 12.
The reprogramming of fibroblasts to induced pluripotent stem cells raises the possibility that somatic cells could be directly reprogrammed to cardiac progenitor cells (CPCs). The present study aimed to assess highly efficient protein-based approaches to reduce or eliminate the genetic manipulations to generate CPCs for cardiac regeneration therapy. A combination of QQ-reagent-modified Gata4, Hand2, Mef2c, and Tbx5 and three cytokines rapidly and efficiently reprogrammed human dermal fibroblasts (HDFs) into CPCs. This reprogramming process enriched trimethylated histone H3 lysine 4, monoacetylated histone H3 lysine 9, and Baf60c at the Nkx2.5 cardiac enhancer region by the chromatin immunoprecipitation quantitative polymerase chain reaction assay. Protein-induced CPCs transplanted into rat hearts after myocardial infarction improved cardiac function, and this was related to differentiation into cardiomyocyte-like cells. These findings demonstrate that the highly efficient protein-transduction method can directly reprogram HDFs into CPCs. This protein reprogramming strategy lays the foundation for future refinements both in vitro and in vivo and might provide a source of CPCs for regenerative approaches.
The findings from the present study have demonstrated an efficient protein-transduction method of directly reprogramming fibroblasts into cardiac progenitor cells. These results have great potential in cell-based therapy for cardiovascular diseases.
成纤维细胞重编程为诱导多能干细胞增加了体细胞可直接重编程为心脏祖细胞（CPC）的可能性。本研究旨在评估基于蛋白质的高效方法，以减少或消除用于心脏再生治疗的CPC生成过程中的基因操作。QQ试剂修饰的Gata4、Hand2、Mef2c和Tbx5与三种细胞因子的组合可快速有效地将人皮肤成纤维细胞（HDF）重编程为CPC。通过染色质免疫沉淀定量聚合酶链反应分析，该重编程过程使Nkx2.5心脏增强子区域的三甲基化组蛋白H3赖氨酸4、单乙酰化组蛋白H3赖氨酸9和Baf60c富集。心肌梗死后移植到大鼠心脏的蛋白质诱导CPC改善了心脏功能，这与分化为心肌样细胞有关。这些发现表明，高效的蛋白质转导方法可将HDF直接重编程为CPC。这种蛋白质重编程策略为未来体外和体内的改进奠定了基础，并可能为再生方法提供CPC来源。
本研究结果证明了一种将成纤维细胞直接重编程为心脏祖细胞的高效蛋白质转导方法。这些结果在心血管疾病的细胞治疗中具有巨大潜力。
