title: Effect of bone marrow-derived extracellular matrix on cardiac function after ischemic injury.
abstract: Ischemic heart disease is a leading cause of death, with few options to retain ventricular function following myocardial infarction. Hematopoietic-derived progenitor cells contribute to angiogenesis and tissue repair following ischemia reperfusion injury. Motivated by the role of bone marrow extracellular matrix (BM-ECM) in supporting the proliferation and regulation of these cell populations, we investigated BM-ECM injection in myocardial repair. In BM-ECM isolated from porcine sternum, we identified several factors important for myocardial healing, including vascular endothelial growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-BB. We further determined that BM-ECM serves as an adhesive substrate for endothelial cell proliferation. Bone marrow ECM was injected in a rat model of myocardial infarction, with and without a methylcellulose carrier gel. After one day, reduced infarct area was noted in rats receiving BM-ECM injection. After seven days we observed improved fractional shortening, decreased apoptosis, and significantly lower macrophage counts in the infarct border. Improvements in fractional shortening, sustained through 21 days, as well as decreased fibrotic area, enhanced angiogenesis, and greater c-kit-positive cell presence were associated with BM-ECM injection. Notably, the concentrations of BM-ECM growth factors were 10(3)-10(8) fold lower than typically required to achieve a beneficial effect, as reported in pre-clinical studies that have administered single growth factors alone.
authors: Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, GA 30332, USA.
authors: Swathi
authors: S
authors: Ravi
authors: Jeffrey M
authors: JM
authors: Caves
authors: Adam W
authors: AW
authors: Martinez
authors: Jiantao
authors: J
authors: Xiao
authors: Jing
authors: J
authors: Wen
authors: Carolyn A
authors: CA
authors: Haller
authors: Michael E
authors: ME
authors: Davis
authors: Elliot L
authors: EL
authors: Chaikof
mesh_terms: D000818:Animals; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism*; D006334:Heart Function Tests; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008747:Methylcellulose / Q000737:chemistry; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D033581:Stem Cell Transplantation; D034421:Sus scrofa
chemical_list: D008747:Methylcellulose