title: Embryonic Stem Cells and Released Factors Stimulate c-kit(+)/FLK-1(+) Progenitor Cells and Promote Neovascularization in Doxorubicin-Induced Cardiomyopathy.
abstract: Vascular apoptosis plays a pivotal role in the development and progression of a myriad of cardiac dysfunctions, but has yet to be investigated in doxorubicin-induced cardiomyopathy (DIC). Additionally, the neovascularization potential and resulting functional consequences of embryonic stem (ES) cells and factors released from these cells in the chronic DIC myocardium remain largely unknown. To this end, we transplanted conditioned media (CM) and ES cells in the DIC-injured heart and evaluated their potential to inhibit vascular cell death, activate endogenous c-kit(+) and FLK-1(+) cells, enhance neovascularization, and augment left ventricular dysfunction. Data presented suggest transplanted CM and ES cells significantly blunt vascular cell apoptosis consequent to DIC. Quantitative immunohistochemistry data demonstrate significantly increased c-kit(+) and FLK-1(+) cells, as well as enhanced differentiated CD31(+) cells in the CM and ES cell groups relative to DIC controls. Heart function, including fractional shortening and ejection fraction, assessed by transthoracic echocardiography, was significantly improved following CM and ES cell transplantation. In conclusion, our data suggest that transplantation of CM and ES cells inhibit vascular apoptosis, activate endogenous c-kit(+) and FLK-1(+) cells and differentiate them into endothelial cells, enhance neovascularization, and improve cardiac function in the DIC-injured myocardium.
authors.affiliation: Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.
authors.forename: Dinender K
authors.initials: DK
authors.lastname: Singla
authors.forename: Latifa S
authors.initials: LS
authors.lastname: Abdelli
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000254:growth & development; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D002908:Chronic Disease; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D006334:Heart Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D033581:Stem Cell Transplantation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D004317:Doxorubicin; D019009:Proto-Oncogene Proteins c-kit; D040301:Vascular Endothelial Growth Factor Receptor-2