RRC ID 43528
Author Takehara N, Tsutsumi Y, Tateishi K, Ogata T, Tanaka H, Ueyama T, Takahashi T, Takamatsu T, Fukushima M, Komeda M, Yamagishi M, Yaku H, Tabata Y, Matsubara H, Oh H.
Title Controlled delivery of basic fibroblast growth factor promotes human cardiosphere-derived cell engraftment to enhance cardiac repair for chronic myocardial infarction.
Journal J Am Coll Cardiol
Abstract 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.
Volume 52(23)
Pages 1858-1865
Published 2008-12-2
DOI 10.1016/j.jacc.2008.06.052
PII S0735-1097(08)03105-7
PMID 19038683
MeSH Animals Bone Marrow Cells / cytology Cell Differentiation Cell Transplantation / methods* Fibroblast Growth Factor 2 / administration & dosage Fibroblast Growth Factor 2 / metabolism* Heart / physiology* Humans Mesenchymal Stem Cells / cytology Models, Biological Myocardial Infarction / therapy* Myocardial Reperfusion Placebos Random Allocation Reperfusion Swine
IF 18.639
Times Cited 154
Human and Animal Cells