TY - JOUR
T1 - Controlled Delivery of Basic Fibroblast Growth Factor Promotes Human Cardiosphere-Derived Cell Engraftment to Enhance Cardiac Repair for Chronic Myocardial Infarction
AU - Takehara, Naofumi
AU - Tsutsumi, Yoshiaki
AU - Tateishi, Kento
AU - Ogata, Takehiro
AU - Tanaka, Hideo
AU - Ueyama, Tomomi
AU - Takahashi, Tomosaburo
AU - Takamatsu, Tetsuro
AU - Fukushima, Masanori
AU - Komeda, Masashi
AU - Yamagishi, Masaaki
AU - Yaku, Hitoshi
AU - Tabata, Yasuhiko
AU - Matsubara, Hiroaki
AU - Oh, Hidemasa
N1 - Funding Information:
Supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology, and by grants-in-aid from the Ministry of Health, Labor, and Welfare. Drs. Tabata and Oh have applied for patents. Drs. Takehara and Tsutsumi contributed equally to this work.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/12/2
Y1 - 2008/12/2
N2 - 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.
AB - 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.
KW - bFGF
KW - cell therapy
KW - gelatin hydrogel
KW - heart failure
KW - myocardial infarction
UR - http://www.scopus.com/inward/record.url?scp=56349146612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56349146612&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2008.06.052
DO - 10.1016/j.jacc.2008.06.052
M3 - Article
C2 - 19038683
AN - SCOPUS:56349146612
SN - 0735-1097
VL - 52
SP - 1858
EP - 1865
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 23
ER -