Millipore Home

• Home
• Products
• Services
• Learning Center
• Tech Library
• Support
• Company

Product Reference

Pre-treatment of mesenchymal stem cells with a combination of growth factors enhances gap junction formation, cytoprotective effect on cardiomyocytes, and therapeutic efficacy for myocardial infarction.

Author	Joo-Yong Hahn, Hyun-Ju Cho, Hyun-Jae Kang, Tack-Seung Kim, Mi-Hyung Kim, Jung-Hwa Chung, Jang-Whan Bae, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Citation Information	Journal of the American College of Cardiology, 51:933-43 (2008)
Keywords	Animals, Bone Morphogenetic Protein 2, Bone Morphogenetic Proteins, Cell Differentiation, Disease Models, Animal, Fibroblast Growth Factor 2, Gap Junctions, Gene Expression, Insulin-Like Growth Factor I, Male, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells, Myocardial Infarction, Myocytes, Cardiac, Rats, Rats, Inbred F344, Transforming Growth Factor beta
Related Products	S7100
Pub Med ID	18308163

OBJECTIVES: The goal of this study was to investigate the effect of pre-treatment of mesenchymal stem cells (MSCs) with growth factors (GFs) on cardiomyogenic differentiation, cytoprotective action on cardiomyocytes (CMCs), and their therapeutic efficacy in myocardial infarction. BACKGROUND: Mechanisms of myocardial repair with MSC transplantation have not been fully elucidated, and therapeutic efficacy needs to be enhanced. METHODS: The MSCs obtained from the bone marrow of Fisher344 rats were treated with fibroblast growth factor-2, insulin-like growth factor-1, and bone morphogenetic protein-2. The expression of cardiac specific markers and the cytoprotective effect of MSCs with its mechanism were evaluated. Efficacy of MSCs transplantation was studied in rat myocardial infarction model. RESULTS: Treatment of MSCs with cocktails of GFs enhanced expression of cardiac transcription factors and survival. Induction of cardiac specific markers by coculture with CMCs and gap junctional communication with CMCs was more active in GF-treated MSCs than untreated MSCs. The GF-treated MSCs reduced apoptosis of neighboring CMCs in a hypoxic condition and enhanced the phosphorylated Akt and phosphorylated c-AMP response element binding protein expression of CMCs, which was markedly reduced by gap junction blockade. In a rat myocardial infarction model, transplantation of GF-treated MSCs resulted in smaller infarct size and better cardiac function than transplantation of untreated MSCs. Additionally, GF treatment enhanced gap junction formation of transplanted MSCs, which did not aggravate arrhythmia. CONCLUSIONS: Pre-treatment of MSCs with GFs enhanced cytoprotective effects on neighboring CMCs through gap junction and improved the therapeutic efficacy of MSC transplantation for myocardial repair. Priming of MSCs with GFs before transplantation might improve the therapeutic efficacy of cell therapy.