Epicardium-Derived Tbx18+ CDCs Transplantation Improve Heart Function in Infarcted Mice

Zhenglong Guo; Mengyuan Geng; Litao Qin; Bingtao Hao; Shixiu Liao

doi:10.3389/fcvm.2021.744353

Epicardium-Derived Tbx18⁺ CDCs Transplantation Improve Heart Function in Infarcted Mice

Front Cardiovasc Med. 2022 Jan 24:8:744353. doi: 10.3389/fcvm.2021.744353. eCollection 2021.

Authors

Zhenglong Guo¹, Mengyuan Geng², Litao Qin¹, Bingtao Hao^{1

3}, Shixiu Liao¹

Affiliations

¹ Henan Medical Genetics Institute, Henan Provincial Key Laboratory of Genetic Diseases and Functional Genomics, National Health Commission Key Laboratory of Birth Defects Prevention, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
² School of Medical Laboratory and Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases, Tianjin Medical University, Tianjin, China.
³ School of Basic Medical Sciences, Cancer Research Institute, Southern Medical University, Guangzhou, China.

Abstract

Cardiosphere-derived cells (CDCs) constitute a cardiac stem cell pool, a promising therapeutics in treating myocardial infarction (MI). However, the cell source of CDCs remains unclear. In this study, we isolated CDCs directly from adult mouse heart epicardium named primary epicardium-derived CDCs (pECDCs), which showed a different expression profile compared with primary epicardial cells (pEpiCs). Interestingly, pECDCs highly expressed T-box transcription factor 18 (Tbx18) and showed multipotent differentiation ability in vitro. Human telomerase reverse transcriptase (hTERT) transduction could inhibit aging-induced pECDCs apoptosis and differentiation, thus keeping a better proliferation capacity. Furthermore, immortalized epicardium CDCs (iECDCs) transplantation extensively promote cardiogenesis in the infracted mouse heart. This study demonstrated epicardium-derived CDCs that may derive from Tbx18⁺ EpiCs, which possess the therapeutic potential to be applied to cardiac repair and regeneration and suggest a new kind of CDCs with identified origination that may be followed in the developing and injured heart.

Keywords: CDCs; Tbx18; epicardial cells; epicardium; hTERT; myocardial infarction.