Controlled Delivery of Basic Fibroblast Growth Factor Promotes Human Cardiosphere-Derived Cell Engraftment to Enhance Cardiac Repair for Chronic Myocardial Infarction

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:52

Article

Takehara, Naofumi¹  Tsutsumi, Yoshiaki⁵  Tateishi, Kento^1,5  Ogata, Takehiro¹  Tanaka, Hideo⁶  Ueyama, Tomomi¹  Takahashi, Tomosaburo^1,5  Takamatsu, Tetsuro⁶  Fukushima, Masanori²  Komeda, Masashi⁴  Yamagishi, Masaaki⁷  Yaku, Hitoshi⁷  Tabata, Yasuhiko³  Matsubara, Hiroaki^1,5  Oh, Hidemasa¹ 

[1] Kyoto Univ, Dept Expt Therapeut, Kyoto, Japan

[2] Kyoto Univ, Translat Res Ctr, Div Clin Trial Design & Management, Kyoto, Japan

[3] Kyoto Univ, Inst Frontier Med Sci, Dept Biomat, Kyoto, Japan

[4] Toyohashi Heart Ctr, Dept Cardiovasc Surg, Toyohashi, Aichi, Japan

[5] Kyoto Prefectural Univ Med, Dept Cardiovasc Med, Kyoto, Japan

[6] Kyoto Prefectural Univ Med, Dept Pathol & Cell Regulat, Kyoto, Japan

[7] Kyoto Prefectural Univ Med, Dept Cardiovasc Surg, Kyoto, Japan

关键词: cell therapy;    bFGF;    gelatin hydrogel;    heart failure;    myocardial infarction;   

DOI  :  10.1016/j.jacc.2008.06.052

来源: Elsevier

【 摘 要 】

Objectives This study was designed to determine whether controlled release of basic fibroblast growth factor ( bFGF) might improve human cardiosphere-derived cell (hCDC) therapy in a pig model of chronic myocardial infarction. Background Current cell therapies for cardiac repair are limited by loss of the transplanted cells and poor differentiation. Methods We conducted 2 randomized, placebo-controlled studies in immunosuppressed pigs with anterior myocardial infarctions. Four weeks after coronary reperfusion, 14 pigs were randomly assigned to receive an intramyocardial injection of placebo medium with or without bFGF-incorporating hydrogel implantation. As a second study, 26 pigs were randomized to receive controlled release of bFGF combined with or without hCDCs or bone marrow-derived mesenchymal stem cell transplantation 4 weeks after reperfusion. Results Controlled release of bFGF in ischemic myocardium significantly augmented the formation of microvascular networks to enhance myocardial perfusion and contractile function. When combined with cell transplantation, the additive effects of bFGF were confined to hCDC-injected animals, but were not observed in animals receiving human bone marrow-derived mesenchymal stem cell transplantation. This was shown by increased donor-cell engraftment and enhanced cardiomyocyte differentiation in the transplanted hearts, resulting in synergistically improved ventricular function and regional wall motion and reduced infarct size. Conclusions Controlled delivery of bFGF modulates the post-ischemic microenvironment to enhance hCDC engraftment and differentiation. This novel strategy demonstrates significant functional improvements after myocardial infarction and may potentially represent a therapeutic approach to be studied in a clinical trial in human heart failure. (J Am Coll Cardiol 2008; 52: 1858-65) (c) 2008 by the American College of Cardiology Foundation

【 授权许可】

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