Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
Biomaterials. 2013 Jan;34(1):92-9. doi: 10.1016/j.biomaterials.2012.09.069. Epub 2012 Oct 13.
Human bone marrow-derived mesenchymal stem cells (hMSCs) are an attractive candidate for cell therapy in heart disease. Low survival and incomplete electromechanical integration between resident cardiomyocytes and transplanted hMSCs remain unsolved. In order for an infarcted heart to tolerate transplantation, differentiation capacity in stem cells must be reinforced. In this study, we found that compound 56, an epidermal growth factor receptor (EGFR) inhibitor, promotes cardiogenic differentiation of hMSCs and the transplantation of hMSCs treated with compound 56 resulted in enhancement of heart functions. Furthermore, hMSCs transfected with microRNA-133a (miR-133a), which targets EGFR, were observed to express cardiac-specific markers. We also discovered that luciferase activity is exclusively decreased by targeting EGFR in hMSCs transfected with miR-133a mimic. These results suggest that EGFR plays a key role in the regulation of cardiogenic differentiation in hMSCs.
人骨髓间充质干细胞（hMSCs）是心脏病细胞治疗的有吸引力的候选物。驻留心肌细胞与移植的 hMSCs 之间的低存活率和不完全的机电整合仍然未得到解决。为了使梗死的心脏能够耐受移植，干细胞的分化能力必须得到加强。在这项研究中，我们发现表皮生长因子受体（EGFR）抑制剂化合物 56 可促进 hMSCs 的心脏分化，并且用化合物 56 处理的 hMSCs 的移植导致心脏功能增强。此外，转染靶向 EGFR 的 microRNA-133a（miR-133a）的 hMSCs 观察到表达心脏特异性标志物。我们还发现，转染 miR-133a 模拟物的 hMSCs 中，荧光素酶活性仅通过靶向 EGFR 而降低。这些结果表明 EGFR 在 hMSCs 的心脏分化调节中起关键作用。
