| Project/Area Number |
13470152
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kansai Medical University |
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Principal Investigator |
MATSUBARA Hiroaki Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10239072)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIHATA Hiroshi Kansai Medical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60233946)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 2002: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2001: ¥10,600,000 (Direct Cost: ¥10,600,000)
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| Keywords | angiogenesis / stem cells / regenerative medicine / bone marrow / vasculogenesis / regeneration / 血管再生 / 狭心症 / ASO |
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| Research Abstract |
Therapeutic angiogenesis by transplantation of autologous bone marrow mononuclear cells(BM-MNC) was established in 103 patients with ischemic limbs by multi-center study(TACT-1 Study Group) in Japan. Safety and efficacy was approved with 2-year follow-up study(22 patients). CD34^+ cells expressed bFGF>>VEGF>angiopoietin-1, while CD34^+ cells predominantly expressed their receptors. In BM-MNC-implanted limbs, ankle-brachial pressure index(ABI) was increased from 0.57 at baseline to 0.66 at week 4 and 0.64 at week 24 (P<0.0001). Rest pain in ischemic limbs was regressed in 70 of 84 patients, and their pain-limited treadmill walking time was significantly improved(from 1.4 min at baseline to 3.6 at week 4 and 4.2 at week 24,P<0.0001). Ischemic ulcers or gangrenes were healed in 54 of 73 limbs including successful limb salvage. Immunohistochemical analysis revealed a striking increase in new capillary formation with Ki-67 positive proliferating endothelial cells. On basis of the results of TACT-1 Study and pre-clinical experiments using porcine models, we performed the clinical trial of a sole cell therapy using catheter-based BM-MNC implantation in three no-option patients(n=3) with ischemic hibernating myocardium. 0.2 ml of BM-MNC was injected into 20 different sites(total 1x10^8 cells) via catheter with a 27G needle. Angina occurrence decreased dramatically and improvement in wall motion was observed in ischemic area with regional perfusion(SPECT, NOGA ventriography). There was no substantial arrhythmia on 24 h Holter recordings performed monthly for 1.5 year. Thus, cell-based investigational therapies for ischemic heart diseases were shown to be safe and feasible.
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