He Xu, Wang Xin-rui, Yang Xu-fang, Zhang Li-hong, Niu Yun, Li Yu-lin
The Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
Zhonghua Bing Li Xue Za Zhi. 2010 Jul;39(7):458-62.
The effect of human bone marrow mesenchymal stem cells (hMSCs) on tumor neovascularization were studied.
hMSCs were isolated from human bone marrow by density gradient fractionation and adherence to plastic flasks. hMSCs-EGFP were obtained by pLEGFP-N1 retroviral vector. Flow cytometry was used to detect the cell surface antigen and the differentiation potential of hMSCs-EGFP was investigated under conditioned media. The effect of hMSCs on tumor neovascularization were observed by establishing solid tumor models in BALB/C nude mice. In addition, effect of the conditioned medium used for tumor cells and endothelial cells (EC) cultivation was collected, to detect its effect on the growth and migration rates of hMSC. hMSCs were induced to differentiate into EC in vitro and the migratory effect on HUVEC was also evaluated.
hMSCs-EGFP, like hMSC, exhibited a fibroblast-like morphological feature, and both had the similar cell surface antigens. They could be induced into osteocytes or adipocytes under the conditioned media. The results not only suggested that hMSCs contributed to tumor neovascularization, but also indicated that most of vessels were host-derived angiogenesis mediated by hMSCs. The mean vascular density (MVD) in suspension group (13.67 ± 1.53) was strikely higher than that in MCF-7 group (5.33 ± 1.42), which showed statistical significance (P < 0.05). Only very few vessels were attributed to hMSCs transdifferentiation into ECs. Tumor cells and ECs can promote hMSCs proliferation and migration through paracrine action. Furthermore, hMSCs were positive for CD31 after 2 weeks induction and HUVEC migration can be facilitated by hMSCs.
MSCs have the effect of promoting tumor neovascularization.
研究人骨髓间充质干细胞（hMSCs）对肿瘤新生血管形成的影响。
通过密度梯度离心和贴壁于塑料培养瓶从人骨髓中分离hMSCs。通过pLEGFP - N1逆转录病毒载体获得hMSCs - EGFP。采用流式细胞术检测细胞表面抗原，并在条件培养基下研究hMSCs - EGFP的分化潜能。通过在BALB/C裸鼠中建立实体瘤模型观察hMSCs对肿瘤新生血管形成的影响。此外，收集用于培养肿瘤细胞和内皮细胞（EC）的条件培养基，检测其对hMSC生长和迁移率的影响。体外诱导hMSCs分化为EC，并评估其对人脐静脉内皮细胞（HUVEC）的迁移作用。
hMSCs - EGFP与hMSC一样呈现成纤维细胞样形态特征，且两者具有相似的细胞表面抗原。在条件培养基下它们可被诱导分化为骨细胞或脂肪细胞。结果不仅表明hMSCs促进肿瘤新生血管形成，还表明大多数血管是由hMSCs介导的宿主来源血管生成。悬浮组的平均血管密度（MVD）（13.67±1.53）显著高于MCF - 7组（5.33±1.42），差异具有统计学意义（P < 0.05）。仅有极少数血管归因于hMSCs转分化为EC。肿瘤细胞和EC可通过旁分泌作用促进hMSCs增殖和迁移。此外，诱导2周后hMSCs的CD31呈阳性，且hMSCs可促进HUVEC迁移。
间充质干细胞具有促进肿瘤新生血管形成的作用。
