Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stimulation.
Adipose stem cells (ASCs) are a source of regenerative cells available for autologous transplantation to hearts. We compared protective actions of ASC sheets on rat myocardial infarction (MI) in comparison with those of skeletal myoblast cell sheets. Their effects on infarcted hearts were evaluated by biological, histochemical as well as physiological analyses. ASC sheets secreted higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under normoxic and hypoxic conditions than those of myoblast cell sheets, associated with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was associated with increases in angiogenic factors (P < 0.05). In isolated perfused rat hearts, ASC sheets improved both systolic and diastolic functions, which was comparable to cardiac functions of myoblast cell sheets, while both cell sheets failed to restore cardiac contractile response to either isoproterenol, pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved cardiac function and remodeling of MI hearts mediated by their paracrine action and this improvement was comparable to those by myoblast cell sheets.
Division of Organ Regeneration Surgery, Tottori University Faculty of Medicine.
Yuki
Y
Otsuki
Yoshinobu
Y
Nakamura
Shingo
S
Harada
Yasutaka
Y
Yamamoto
Kazuhide
K
Ogino
Kumi
K
Morikawa
Haruaki
H
Ninomiya
Shigeru
S
Miyagawa
Yoshiki
Y
Sawa
Ichiro
I
Hisatome
Motonobu
M
Nishimura
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D064752:Atrial Remodeling / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002454:Cell Differentiation; D003971:Diastole / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques; D019899:Paracrine Communication / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013599:Systole / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D011724:Pyridazines; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C041648:pimobendan; D005346:Fibroblast Growth Factors; D003994:Bucladesine; D017228:Hepatocyte Growth Factor; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol