title: Primary adipose-derived stem cells enriched by growth factor treatment improves cell adaptability toward cardiovascular differentiation in a rodent model of acute myocardial infarction.
abstract: The heterogeneous cell population in primary adipose-derived adult stem cells (ADAS) and difficulty in keeping their primitive properties have posed certain limitations on using these cells for cell therapy. Therefore, our objective was to generate a population of cells enriched from the adipose stromal-vascular fraction (SVF) with greater differentiation potential than ADAS and to explore the mechanism behind the repair of the injured myocardium in vivo. The distinct population of adipose stromal cells was enriched by immediate treatment of the growth factor cocktail (EGF and PDGF-BB) to the freshly isolated SVF. These cells (ADAS-GFs) had distinct cell morphology from ADAS and in average had a smaller size. They presented co-expression of CD140a (pericytic markers) and CD34 (hematopoietic marker), more obvious mesenchymal (CD13, CD29, CD44, CD90 and CD117) markers, but rare KDR, and were negative for CD45 and CD31. ADAS-GFs not only spontaneously expressed endothelial cell markers and formed capillary-like tubes on Matrigel but also clearly expressed early cardiomyocyte marker genes when embedded in methylcellulose-based medium. In Sprague-Dawley (SD) rats with left anterior descending artery (LAD)-induced myocardial infarction (MI), the ADAS-GFs transplanted group had the left ventricular function significantly improved compared with the ADAS transplanted group or the control group at 12 weeks post transplantation. The immunofluorescence staining revealed that the transplanted ADAS-GFs expressed GATA4, betamyosin heavy chain and troponin T protein but not vWF. More capillaries were also observed around the infarcted zone in the ADAS-GFs transplanted group. These data suggested that ADAS-GFs with a higher proangiogenic potential may restore the cardiac function of infarcted myocardium via the direct cardiomyocyte differentiation as well as angiogenesis recruitment.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 40227, Taiwan.
authors.forename: Jui-Chih
authors.initials: JC
authors.lastname: Chang
authors.forename: Ping-Chun
authors.initials: PC
authors.lastname: Lee
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Kung-Wei
authors.initials: KW
authors.lastname: Lee
authors.forename: Shan-hui
authors.initials: SH
authors.lastname: Hsu
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin; D004815:Epidermal Growth Factor