2. Academic Validation
  3. Reprogramming of fibroblasts into expandable cardiovascular progenitor cells via small molecules in xeno-free conditions

Reprogramming of fibroblasts into expandable cardiovascular progenitor cells via small molecules in xeno-free conditions

  • Nat Biomed Eng. 2022 Apr;6(4):403-420. doi: 10.1038/s41551-022-00865-7.
Jia Wang  # 1 2,  Shanshan Gu  # 1 2,  Fang Liu 1 2,  Zihao Chen 1 2,  He Xu 1 2,  Zhun Liu 1 2,  Weisheng Cheng 1 2,  Linwei Wu 1 2,  Tao Xu 1 2,  Zhongyan Chen 1 2,  Ding Chen 1 2,  Xuena Chen 1 2,  Fanzhu Zeng 1 2,  Zhiju Zhao 1 2,  Mingliang Zhang 3,  Nan Cao 4 5
Affiliations

Affiliations

  • 1 Zhongshan School of Medicine and the Seventh Affiliated Hospital, Sun Yat-Sen University, Guangdong, China.
  • 2 Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangdong, China.
  • 3 Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Reproductive Medicine, Shanghai, China.
  • 4 Zhongshan School of Medicine and the Seventh Affiliated Hospital, Sun Yat-Sen University, Guangdong, China. caon3@mail.sysu.edu.cn.
  • 5 Key Laboratory for Stem Cells and Tissue Engineering (Sun Yat-Sen University), Ministry of Education, Guangdong, China. caon3@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 35361933 DOI: 10.1038/s41551-022-00865-7
Abstract

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.

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