Jang Hyeon-Ki, Kim Byung-Soo, Han Jin, Yoon Jeong-Kee, Lee Ju-Ro, Jeong Gun-Jae, Shin Jung-Youn
Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, 151-744, Republic of Korea.
School of Chemical and Biological Engineering, Seoul National University, Seoul, 151-744, Republic of Korea.
Biotechnol Prog. 2016 Mar;32(2):456-64. doi: 10.1002/btpr.2226. Epub 2016 Jan 23.
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. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:456-464, 2016.
干细胞条件培养基（CM）含有干细胞分泌的血管生成因子，是一种治疗缺血性疾病的潜在疗法。与干细胞一样，肿瘤细胞也分泌多种血管生成因子。在此，评估了肿瘤细胞作为用于治疗性血管生成的CM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。将人纤维肉瘤HT1080细胞系培养物获得的CM与源自人骨髓的间充质干细胞（MSC）培养物获得的CM进行比较。与MSC CM相比，HT1080 CM含有更高浓度的血管生成因子，这归因于HT1080细胞比MSC生长速度快得多，从而导致更高的细胞密度。为用于体外和体内血管生成研究，对HT1080 CM进行稀释，以使HT1080 CM和MSC CM具有相同的细胞数量基础。两种类型的CM在体外诱导人脐静脉内皮细胞（HUVEC）增殖的程度相同。与注射新鲜培养基相比，将HT1080 CM注射到小鼠缺血肢体中可显著改善毛细血管密度和血液灌注。尽管HT1080 CM的治疗效果与MSC CM相似，但由于肿瘤细胞系生长更快且寿命无限，通过肿瘤细胞系培养制备CM的效率会更高。这些数据表明肿瘤细胞CM作为血管生成和缺血性疾病治疗方式的潜在应用。©2016美国化学工程师学会生物技术进展，32:456 - 464，2016。
