title: Cardiac Adipose-Derived Stem Cells Exhibit High Differentiation Potential to Cardiovascular Cells in C57BL/6 Mice.
abstract: Adipose-derived stem cells (AdSCs) have recently been shown to differentiate into cardiovascular lineage cells. However, little is known about the fat tissue origin-dependent differences in AdSC function and differentiation potential. AdSC-rich cells were isolated from subcutaneous, visceral, cardiac (CA), and subscapular adipose tissue from mice and their characteristics analyzed. After four different AdSC types were cultured with specific differentiation medium, immunocytochemical analysis was performed for the assessment of differentiation into cardiovascular cells. We then examined the in vitro differentiation capacity and therapeutic potential of AdSCs in ischemic myocardium using a mouse myocardial infarction model. The cell density and proliferation activity of CA-derived AdSCs were significantly increased compared with the other adipose tissue-derived AdSCs. Immunocytochemistry showed that CA-derived AdSCs had the highest appearance rates of markers for endothelial cells, vascular smooth muscle cells, and cardiomyocytes among the AdSCs. Systemic transfusion of CA-derived AdSCs exhibited the highest cardiac functional recovery after myocardial infarction and the high frequency of the recruitment to ischemic myocardium. Moreover, long-term follow-up of the recruited CA-derived AdSCs frequently expressed cardiovascular cell markers compared with the other adipose tissue-derived AdSCs. Cardiac adipose tissue could be an ideal source for isolation of therapeutically effective AdSCs for cardiac regeneration in ischemic heart diseases. Significance: The present study found that cardiac adipose-derived stem cells have a high potential to differentiate into cardiovascular lineage cells (i.e., cardiomyocytes, endothelial cells, and vascular smooth muscle cells) compared with stem cells derived from other adipose tissue such as subcutaneous, visceral, and subscapular adipose tissue. Notably, only a small number of supracardiac adipose-derived stem cells that were systemically transplanted sufficiently improved cardiac functional recovery after myocardial infarction, differentiating into cardiovascular cells in the ischemic myocardium. These findings suggest a new autologous stem cell therapy for patients with myocardial ischemia, especially those with secondary myocardial ischemia after cardiovascular open chest surgery.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka, Japan Department of Internal Medicine (I), Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagata
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka, Japan masaii@osaka-med.ac.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ii
authors.affiliation: Department of Internal Medicine (I), Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Kohbayashi
authors.affiliation: Department of Internal Medicine (III), Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hoshiga
authors.affiliation: Department of Internal Medicine (I), Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Asahi
mesh_terms: D050153:Abdominal Fat / Q000166:cytology / Q000378:metabolism; D017667:Adipocytes / Q000145:classification / Q000166:cytology* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D006348:Cardiac Surgical Procedures; D002452:Cell Count; D002454:Cell Differentiation; D002469:Cell Separation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D050151:Subcutaneous Fat / Q000166:cytology / Q000378:metabolism; D014182:Transplantation, Autologous
chemical_list: D015415:Biomarkers
keywords: Adipose stem cells; Cardiac; Differentiation; Stem cell transplantation