title: Generation of Functional Human Cardiac Progenitor Cells by High-Efficiency Protein Transduction.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Biochemistry and Molecular Biology Department, Wayne State University School of Medicine, Detroit, Michigan, USA.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Deng
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Zaiyi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Yongheng
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Mengzhen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Honghong
authors.initials: H
authors.lastname: Tan
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Biochemistry and Molecular Biology Department, Wayne State University School of Medicine, Detroit, Michigan, USA yuxycn@aliyun.com jjwang@med.wayne.edu.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangdong Cardiovascular Institute of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, People's Republic of China yuxycn@aliyun.com jjwang@med.wayne.edu.
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D000067470:Cellular Reprogramming Techniques; D016207:Cytokines / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D009203:Myocardial Infarction / Q000378:metabolism / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D016207:Cytokines; D014157:Transcription Factors
keywords: Cardiac differentiation; Cardiac progenitor cells; Cardiac transcription factor; Cell transplantation; Protein