Department of Cardiology, Shantou University, Shantou 515041, People's Republic of China.
Cardiovasc Pathol. 2011 Mar-Apr;20(2):77-83. doi: 10.1016/j.carpath.2009.12.003. Epub 2010 Feb 8.
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.
心肌梗死后充血性心力衰竭是工业化国家发病率和死亡率的主要原因之一。胚胎干细胞是否是梗死心脏中进行原位心脏再生的可行来源仍存在争议。为了研究梗死的心脏微环境是否可以选择性地促进胚胎干细胞分化为心肌细胞，我们评估了注射到正常（n=16）或急性梗死大鼠心脏（n=18）中的小鼠胚胎干细胞（mESC）的心脏分化潜能。我们发现，移植的 4'，6-二脒基-2-苯基吲哚（DAPI）标记的 mESC 能够在正常和梗死心脏中存活并形成稳定的心脏内移植物，并且在移植区域中发现了巨噬细胞。mESC 移植后 2 至 4 周，我们发现与梗死心脏相比，在正常心脏中更多的 DAPI 阳性 mESC 分化为心肌细胞，其标志物为心肌肌钙蛋白 T（cTnT）（2.67±0.79%对 1.06±0.52%，P<.01）。然而，在 4 周后，正常心脏和梗死心脏中 DAPI 阳性细胞表达 cTnT 的百分比之间的差异减小（1.17±0.98%对 1.07±1.02%，P>.05），此时 mESC 衍生的心肌细胞开始出现横纹。此外，mESC 在正常和梗死心脏中分化为波形蛋白阳性的心肌成纤维细胞。我们的结果表明，移植的 mESC 不仅可以在梗死大鼠心脏中存活，而且可以分化为心肌细胞。然而，梗死的心脏微环境不能选择性地促进 mESC 分化为心肌细胞。
