Efficacy and safety of bone-marrow stem cell therapy in the rat with ischemic cardiomyopathy

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591503
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kansai Medical University
• Principal Investigator: IMAMURA Hiroji Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (10118911)
• Co-Investigator(Kenkyū-buntansha): OTANI Hajime Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60168979)
• Project Period (FY): 2003 – 2004
• Keywords: Mesenchymal stem cell / Green fluorescence protein / PI3K / Myocardial infarction / Regeneration therapy

Research Abstract

Background : We hypothesized that mesenchymal stem cell (MSC) engraftment could be improved by increasing survival of MSCs immediately after MSC transplantation (MSCT) using insulin-like growth factor-1 (IGF-1). Methods and Results : Myocardial infarction (MI) in rats was produced by permanent ligature of the left coronary artery. One month after MI, rat hearts were injected with MSCs in the presence or absence of IGF-1 with or without the phosphatidylinositol 3-kinase inhibitor, LY294002. Most of MSCs transplanted at the infarction border were rapidly (within minutes) moved to the apex. Semi-quantitative analysis of the number of MSCs in the infarct area showed that IGF-1 significantly increased the number of MSCs within the infarct area immediately after transplantation and inhibited the death of MSCs at one day after transplantation. However, IGF-1 did not prevent the loss of MSCs thereafter, although the number of MSCs remained in the infarcted area was significantly greater in the IGF-1-treated heart. Transplanted MSCs were not differentiated into cardiomyocytes but were differentiated into osteoblasts 1 month after MSC transplantation. MSC transplantation with IGF-1 significantly increased neovascularization and improved LV function at 1 month after MSCT. LY294002 abrogated all the effect of MSC transplantation with IGF-1. Injection with IGF-1 without MSCs had no effect on neovascularization nor did it improve LV function. Conclusions : These results suggest that IGF-1 increases engraftment of MSCs at the time of transplantation via activation of PI3K and improves efficacy of MSC transplantation.