Guo Long Zhe, Kim Tae-Hee, Han Seongho, Kim Sung-Whan
Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University.
Circ J. 2016;80(4):998-1007. doi: 10.1253/circj.CJ-15-1169. Epub 2016 Feb 5.
Although stem cells have been regarded as a promising therapeutic option, the marginal therapeutic effects of stem cells are limitations that must be overcome for the development of effective cell therapy. This study sought to identify the angio-vasculogenic properties of endothelial differentiated mesenchymal stem cells (MSCs) and to determine whether these cells are effective for vascular repair.
Adipose MSCs were cultured for 10 days under endothelial cell (EC) culture conditions. These endothelial cell differentiated adipose MSCs (EA) and undifferentiated adipose MSCs (UA) were characterized via angiogenesis and adhesion assays. These cells were transplanted into a hindlimb ischemia (HLI) model to determine therapeutic effects and their underlying mechanisms. EA displayed low adhesion and angiogenic properties in vitro compared with UA. When implanted into mouse HLI models, EA exhibited the decreased recovery of blood perfusion in limb ischemia than uncultured UA. Histology data showed that injected EA exhibited lower retention, angiogenic cytokine levels, and neovascularization in vivo than did UA. Short-term differentiated EA display less cell engraftment and angio-vasculogenic potential, and are less effective for peripheral vascular repair than UA.
EC differentiation of MSCs may not present an effective strategy for the promotion of therapeutic neovascularization.
尽管干细胞被视为一种有前景的治疗选择,但干细胞的边际治疗效果是有效细胞治疗发展中必须克服的限制。本研究旨在确定内皮分化间充质干细胞(MSCs)的血管生成特性,并确定这些细胞是否对血管修复有效。
脂肪间充质干细胞在内皮细胞(EC)培养条件下培养10天。通过血管生成和黏附试验对这些内皮细胞分化的脂肪间充质干细胞(EA)和未分化的脂肪间充质干细胞(UA)进行表征。将这些细胞移植到后肢缺血(HLI)模型中,以确定治疗效果及其潜在机制。与UA相比,EA在体外表现出低黏附性和血管生成特性。当植入小鼠HLI模型时,与未培养的UA相比,EA在肢体缺血中表现出血液灌注恢复降低。组织学数据显示,注射的EA在体内的保留率、血管生成细胞因子水平和新血管形成均低于UA。短期分化的EA表现出较少的细胞植入和血管生成潜力,对外周血管修复的效果不如UA。
间充质干细胞的内皮细胞分化可能不是促进治疗性新血管形成的有效策略。