The infarcted cardiac microenvironment cannot selectively promote embryonic stem cell differentiation into cardiomyocytes

Chen, You-Ren; Li, Yang; Chen, Li; Yang, Xin-Chun; Su, Pi-Xiong; Cai, Jun

doi:10.1016/j.carpath.2009.12.003

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Volume 20, Issue 2 , Pages 77-83, March 2011

The infarcted cardiac microenvironment cannot selectively promote embryonic stem cell differentiation into cardiomyocytes

You-Ren Chen
- Department of Cardiology, The Second Affiliated Hospital to Medical College, Shantou University, Shantou 515041, PR China
- The two authors contributed equally to this work.
Yang Li
- Stem Cell Research Center, Peking University Health Science Center, Beijing 100191, PR China
- The two authors contributed equally to this work.
Li Chen
- Center for Molecular Development and Disease, Institute of Biosciences and Technology, Texas A&M University health Science Center, Houston, TX 77030, USA
Xin-Chun Yang
- Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
Pi-Xiong Su
- Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
- Corresponding authors. Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Jun Cai
- Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China
- Corresponding authors. Department of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing 100020, China.

Received 16 November 2008; received in revised form 15 November 2009; accepted 18 December 2009. published online 01 February 2010.

Abstract

Postinfarct congestive heart failure is one of the leading causes of morbidity and mortality in industrialized countries. It is controversial whether embryonic stem cells are feasible sources for in situ cardiac regeneration in infarcted hearts. In order to investigate whether the infarcted cardiac microenvironment could selectively promote embryonic stem cell differentiation into cardiomyocytes, we assessed the cardiac differentiation potential of mouse embryonic stem cells (mESCs) injected into normal (n=16) or acutely infarcted rat hearts (n=18). We found that the transplanted 4′,6-diamidino-2-phenylindole (DAPI)-labeled mESCs were able to survive and form stable intracardiac grafts both in normal and infarcted hearts, along with macrophages found specifically in the engraftment area. Two to four weeks after mESC transplantation, we found that more DAPI-positive mESCs differentiated into cardiomyocytes, marked by cardiac troponin T (cTnT), in normal than those in infarcted hearts (2.67±0.79% vs. 1.06±0.52%, P<.01). However, the discrepancy between the percentage of DAPI-positive cells that express cTnT in normal and that in infarcted hearts was diminished after 4 weeks (1.17±0.98% vs. 1.07±1.02%, P>.05), when the transverse striation began to present in the mESCs-derived cardiomyocytes. In addition, mESCs differentiated into vimentin-positive cardiac fibroblasts in normal and infracted hearts. Our results indicated that transplanted mESCs cannot only survive but differentiate into cardiomyocytes in infarcted rat hearts. However, the infarcted cardiac microenvironment cannot selectively promote mESCs differentiation into cardiomyocytes.

Keywords: Embryonic stem cells, Differentiation, Microenvironment, Myocardial infarction, Transplantation