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Therapeutic angiogenesis using tumor cell-conditioned medium

机译:使用肿瘤细胞条件培养基的治疗性血管生成

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Stem cell-conditioned medium (CM), which contains angiogenic factors that are secreted by stem cells, represents a potential therapy for ischemic diseases. Along with stem cells, tumor cells also secrete various angiogenic factors. Here, tumor cells as a cell source of CM for therapeutic angiogenesis was evaluated and the therapeutic efficacy of tumor cell CM in mouse hindlimb ischemia models was demonstrated. CM obtained from a human fibrosarcoma HT1080 cell line culture was compared with CM obtained from a human bone marrow-derived mesenchymal stem cell (MSC) culture. HT1080 CM contained higher concentrations of angiogenic factors compared with MSC CM, which was attributable to the higher cell density that resulted from a much faster growth rate of HT1080 cells compared with MSCs. For use in in vitro and in vivo angiogenesis studies, HT1080 CM was diluted such that HT1080 CM and MSC CM would have the same cell number basis. The two types of CMs induced the same extent of human umbilical vein endothelial cell (HUVEC) proliferation in vitro. The injection of HT1080 CM into mouse ischemic limbs significantly improved capillary density and blood perfusion compared with the injection of fresh medium. Although the therapeutic outcome of HT1080 CM was similar to that of MSC CM, the preparation of CM by tumor cell line culture would be much more efficient due to the faster growth and unlimited life-time of the tumor cell line. These data suggest the potential application of tumor cell CM as a therapeutic modality for angiogenesis and ischemic diseases. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:456-464, 2016
机译:干细胞条件培养基(CM)包含干细胞分泌的血管生成因子,代表了缺血性疾病的潜在疗法。除干细胞外,肿瘤细胞还分泌各种血管生成因子。在这里,评估了肿瘤细胞作为用于治疗血管生成的CM的细胞来源,并证明了肿瘤细胞CM在小鼠后肢缺血模型中的治疗效果。将得自人纤维肉瘤HT1080细胞系培养物的CM与得自人骨髓来源的间充质干细胞(MSC)培养物的CM进行比较。与MSC CM相比,HT1080 CM包含更高浓度的血管生成因子,这归因于HT1080细胞比MSC更快的生长速率导致更高的细胞密度。为了在体外和体内血管生成研究中使用,稀释HT1080 CM,使HT1080 CM和MSC CM具有相同的细胞数基础。两种类型的CM在体外均能诱导相同程度的人脐静脉内皮细胞(HUVEC)增殖。与注入新鲜培养基相比,将HT1080 CM注入小鼠缺血肢体可显着改善毛细血管密度和血液灌注。尽管HT1080 CM的治疗结果与MSC CM相似,但由于肿瘤细胞系的快速生长和无限的寿命,通过肿瘤细胞系培养物制备CM会更加有效。这些数据表明肿瘤细胞CM作为血管生成和缺血性疾病的治疗手段的潜在应用。 (c)2016美国化学工程师学会生物技术学会。 Prog。,32:456-464,2016

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