Somatic Stem Cell Therapy for Cardiovascular Diseases

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  • MATSUBARA Hiroaki
    京都府立医科大学大学院医学系研究科循環器病態制御学,京都大学医学部探索医療センター重症心不全への細胞移植プロジェクト
  • MASAKI Hiroya
    関西医科大学臨床検査医学講座
  • KAMIHATA Hiroshi
    関西医科大学内科学第二講座
  • IWASAKA Toshiji
    関西医科大学内科学第二講座

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  • 体性幹細胞移植と再生医療-末消血管病から心臓病へ-

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Bone marrow cells contain progenitors for vascular endothelial cells (EC) and cardiomyocytes, and also release angiogenic factors (VEGF and bFGF). We have shown availability of implantation of bone marrow mononuclear cells (BMI) for patients with ischemic limbs (Lancet,2002; 360: 427-435). Here, we will talk about the effect of BMI on pig model with chronic ischemic myocardium and 1-year follow-up data for no-option patient (CCS-class-IV angina) treated with sole therapy by BMI. #1) Animal study: Chronic ischemia was prepared by ameroid constrictor in domestic pigs. NOGA electromechanical system was used to map hibernating regions and to inject BMc (30 sites,10 cells). Increases in systolic function (EF: 33 to 52%) and regional blood flow (2.1-fold), reduction of ischemic area (29% to 8%) were observed. Capillary numbers were markedly increased (3.6-fold) with incorporation of BMc, while trans-differentiation into cardiomyocytes was much less (-0.1% of viable myocytes). There was no bone formation (n=15). #2) Clinical Study: A 65-year-old man suffered fr om refractory angina (CCS class IV) in spite of bypass surgery (2 times) and angioplasty (5 times).0.05 ml of BMc was injected into hibernating focus identified by NOGA mapping (30 different sites,3 x 10 cells). Increase in EF (42 to 54%), reduction of ischemic area (16.5% to 3.8%), decrease in angina occurrence (Class IV to I) were observed 10 month after BMI. There was no substantial arrhythmia on 24 h Holter recordings performed monthly for 10 months. Blood supply to ischemic hibernating myocardium and myogenic cell grafting by cell therapy using BMI is a promising approach for prevention of myocardial remodeling.

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