Otsuki Yuki, Nakamura Yoshinobu, Harada Shingo, Yamamoto Yasutaka, Ogino Kazuhide, Morikawa Kumi, Ninomiya Haruaki, Miyagawa Shigeru, Sawa Yoshiki, Hisatome Ichiro, Nishimura Motonobu
Division of Organ Regeneration Surgery, Tottori University Faculty of Medicine.
Biomed Res. 2015;36(1):11-9. doi: 10.2220/biomedres.36.11.
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.
脂肪干细胞(ASC)是可用于心脏自体移植的再生细胞来源。我们将ASC片层对大鼠心肌梗死(MI)的保护作用与骨骼肌成肌细胞片层的保护作用进行了比较。通过生物学、组织化学以及生理学分析评估了它们对梗死心脏的影响。在常氧和低氧条件下,ASC片层分泌的血管生成因子(HGF、VEGF和bFGF;P<0.05)浓度高于成肌细胞片层,且与细胞凋亡减少相关(P<0.05)。与成肌细胞片层一样,ASC片层改善了MI心脏的心脏功能(P<0.05),并降低了血浆中ANP水平(P<0.05)。ASC片层恢复了以纤维化、心脏肥大和血管生成受损为特征的心脏重塑(P<0.05),这与血管生成因子增加相关(P<0.05)。在离体灌注大鼠心脏中,ASC片层改善了收缩和舒张功能,这与成肌细胞片层的心脏功能相当,而两种细胞片层均未能恢复心脏对异丙肾上腺素、匹莫苯丹或二丁酰环磷腺苷的收缩反应。这些结果表明,ASC片层通过其旁分泌作用改善了MI心脏的心脏功能和重塑,且这种改善与成肌细胞片层相当。