Moon Mi Hyang, Kim Sun Young, Kim Yeon Jeong, Kim Su Jin, Lee Jae Bong, Bae Yong Chan, Sung Sang Min, Jung Jin Sup
Department of Physiology, College of Medicine, Pusan National University, Korea.
Cell Physiol Biochem. 2006;17(5-6):279-90. doi: 10.1159/000094140. Epub 2006 Jun 20.
BACKGROUND/AIM: It has been reported that adipose tissue contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. In this study we evaluated the effect of culture-expanded mesenchymal stem cells (MSC) derived from adipose tissue on neovascularization and blood flow in an animal model of limb ischemia in immunodeficient mice.
MSC were cultured from human adipose tissue by collagenase digestion. Hindlimb ischemia was created by ligating the proximal femoral artery of male nude mice. Human adipose tissue stromal cells (hADSC) were transplanted one day or 7 days after ligation.
During culture expansion of hADSC CD34 expression was downregulated. The laser Doppler perfusion index was significantly higher in the CD34(-), Flk-1(-), CD31(-) ADSC-transplanted group than in the control group, even when cells were transplanted 7 days after hindlimb ischemia. Histological examination showed that hADSC transplantation recovered muscle injury and increased vascular density, compared with the control group. The effect of hADSC was correlated with the number of transplanted cells, but not with the ratio of CD34 expression. In vitro, hADSC can form vessel-like structure and express von Willibrand Factor. Conditioned media from hADSC increased proliferation and inhibited apoptotic cell death in of human aortic endothelial cells.
This study showed that hADSC can be an ideal source for therapeutic angiogenesis in ischemic disease.
背景/目的：据报道，脂肪组织含有具有血管生成潜能的祖细胞，基于脂肪组织来源的祖细胞给药的治疗可能成为缺血性疾病患者一种有前景的细胞治疗方法。在本研究中，我们评估了培养扩增的脂肪组织来源的间充质干细胞（MSC）对免疫缺陷小鼠肢体缺血动物模型中新血管形成和血流的影响。
通过胶原酶消化从人脂肪组织中培养MSC。通过结扎雄性裸鼠的股动脉近端制造后肢缺血。在结扎后1天或7天移植人脂肪组织基质细胞（hADSC）。
在hADSC的培养扩增过程中，CD34表达下调。即使在后肢缺血7天后移植细胞，CD34（-）、Flk-1（-）、CD31（-）ADSC移植组的激光多普勒灌注指数也显著高于对照组。组织学检查显示，与对照组相比，hADSC移植可恢复肌肉损伤并增加血管密度。hADSC的作用与移植细胞数量相关，但与CD34表达比例无关。在体外，hADSC可形成血管样结构并表达血管性血友病因子。hADSC的条件培养基可增加人主动脉内皮细胞的增殖并抑制其凋亡性细胞死亡。
本研究表明，hADSC可能是缺血性疾病治疗性血管生成的理想来源。
