| Project/Area Number |
18591566
|
|---|
| 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 (10118911)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OTANI Hajime Kansai Medical University, Faculty of Medicine, Associate Professor (60168979)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | Mesenchymal stem cell / PI3K / Myocardial infarction / Regeneration Therapy / 虚血性心筋症 / 骨髄幹細胞 / 移植・再生医療 / 間葉系幹細胞 / 移殖・再生医療 |
|---|
| Research Abstract |
Background: Improvement of engraftment is a key for successful cell-based therapy. We hypothesized that enhanced mesenchymal cell (MC) engraftment by treatment with insulin-like growth factor 1 (IGF-1) at the time of transplantation can improve left ventricular (LV) function and survival.
Methods and Results: IGF-1 increased phosphatidylinositol 3-kinase (PI3K) activity associated with enhanced adhesion and inhibition of apoptosis of MCs in vitro. Myocardial infarction (MI) in rats was produced by ligature of the left coronary artery and, one month later, the hearts were injected with MCs in the presence or absence of IGF-1 with or without the phosphatidylinositol 3-kinase inhibitor, LY294002. IGF-1 significantly increased engraftment of MCs between 6 hours and 3 days after transplantation, although transplanted MCs were absent one month after transplantation. MC transplantation with IGF-1 significantly increased neovascularization and inhibited cardiomyocyte apoptosis associated with improved left ventricular (LV) function and survival. LY294002 abrogated all the beneficial effects of MC transplantation with IGF-1. IGF-1 alone had no effect on neovascularization, LV function and survival.
Conclusions : These results suggest that IGF-1 increases engraftment of MCs via activation of PI3K at the time of transplantation which enhances neovascularization and inhibits cardiomyocyte death, leading to improvement of LV function and survival.
|
