期刊
CARDIOVASCULAR RESEARCH
卷 95, 期 4, 页码 495-506出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvs224
关键词
Angiogenesis; GCP-2; Mesenchymal stem cells; Myocardial infarction
资金
- Korea Healthcare Technology RD Project
- Ministry of Health and Welfare, Republic of Korea [A070001]
- National Research Foundation of Korea (NRF)
- Korean government (MEST) [2009 0093191]
- National Research Foundation of Korea [2009-0093191] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
In this study, our aim was to evaluate the angio-vasculogenic properties of human adipose tissue-derived mesenchymal stem cells overexpressing the granulocyte chemotactic protein (GCP)-2 (hASCs/GCP-2) and to determine possible therapeutic effects in an experimental ischaemic heart model. Quantitative real-time (qRT)PCR results revealed that hASCs/GCP-2 expressed significantly higher levels of pro-angiogenic genes, including vascular endothelial growth factor (VEGF)-A, hepatocyte growth factor (HGF), and interleukin (IL)-8, when compared with control-vector transduced hASCs or human umbilical vascular endothelial cells (HUVECs). In addition, the anti-apoptotic insulin-like growth factor (IGF)-1 and Akt-1 were also highly up-regulated in the hASCs/GCP-2 cells. In vitro cell migration and proliferation assays showed that hASCs/GCP-2-derived conditioned media (CM) significantly accelerated the migration and proliferation of fibroblast cells. Examination of in vitro endothelial differentiation showed that hASCs/GCP-2 cells spontaneously formed vascular-like structures and highly expressed endothelial-specific genes and proteins. In vivo study results of our mouse myocardial infarction (MI) model revealed that hASCs/GCP-2 implantation improved the cardiac function and reduced the infarct size. Finally, transplanted hASCs/GCP-2 cells unexpectedly differentiated into endothelial cells and the engraftment rate was significantly higher than control groups. We suggest that overexpression of GCP-2 in stem cells has the potential to enhance their angiogenic and survival properties.
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