Optimization and enrichment of induced cardiomyocytes derived from mouse fibroblasts by reprogramming with cardiac transcription factors

Tian,Jiaxin; Wang,Rong; Hou,Qian; Li,Meirong; Chen,Li; Deng,Xiangdong; Zhu,Ziying; Zhao,Yali; He,Wenjun; Fu,Xiaobing

doi:10.3892/mmr.2017.8285

Optimization and enrichment of induced cardiomyocytes derived from mouse fibroblasts by reprogramming with cardiac transcription factors

Authors:
- Jiaxin Tian
- Rong Wang
- Qian Hou
- Meirong Li
- Li Chen
- Xiangdong Deng
- Ziying Zhu
- Yali Zhao
- Wenjun He
- Xiaobing Fu
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Affiliations: Centre for Medical Device Evaluation, China Food and Drug Administration, Beijing 100044, P.R. China, Department of Cardiovascular Surgery, Institute of Cardiac Surgery of PLA, Beijing 100853, P.R. China, Institute of Basic Medicine, Chinese PLA General Hospital, Beijing 100853, P.R. China
Published online on: December 15, 2017 https://doi.org/10.3892/mmr.2017.8285
Pages: 3912-3920

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Abstract

Ischemic heart disease within developed countries has been associated with high rates of morbidity and mortality. Cell‑based cardiac repair is an emerging therapy for the treatment of cardiac diseases; however, a limited source of the optimal type of donor cell, such as an autologous cardiomyocyte, restricts clinical application. The novel therapeutic use of induced pluripotent stem cells (iPSCs) may serve as a unique and unlimited source of cardiomyocytes; however, iPSC contamination has been associated with teratoma formation following transplantation. The present study investigated whether cardiomyocytes from mouse fibroblasts may be reprogrammed in vitro with four cardiac transcription factors, including GATA binding protein 4, myocyte‑specific enhancer factor 2C, T‑box transcription factor 5, and heart‑ and neural crest derivatives‑expressed protein 2 (GMTH). Cardiac‑specific markers, including α‑myosin heavy chain (α‑MHC), β‑MHC, atrial natriuretic factor, NK2 homeobox 5 and cardiac troponin T were observed within mouse fibroblasts reprogrammed with GMTH, which was reported to be more effective than GMT. In addition, Percoll density centrifugation enriched a population of ~72.4±5.5% α‑MHC+ induced cardiomyocytes, which retained the expression profile of cardiomyocyte markers and were similar to natural neonatal cardiomyocytes in well‑defined sarcomeric structures. The findings of the present study provided a potential solution to myocardial repair via a cell therapy applying tissue engineering with minimized risks of immune rejection and tumor formation.

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