Zhang Keqin, Shi Benkang, Chen Jun, Zhang Dongqing, Zhu Yaofeng, Zhou Changkuo, Zhao Haifeng, Jiang Xianzhou, Xu Zhishun
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China.
Urol Int. 2010;84(1):94-9. doi: 10.1159/000273474. Epub 2010 Feb 17.
To investigate the effect of mesenchymal stem cells (MSCs) in the process of tumor development and the possibility of MSCs differentiating into vascular endothelial cells in the tumor microenvironment.
Twenty male New Zealand rabbits were randomly divided into 2 groups: a test group and a control group. MSCs were isolated and cultured by bone marrow cell adherence. The bladder tumor models were built by embedding a VX2 mass in swelled bladder mucosa in all of the rabbits (n = 20). One week later, 4',6-diamidino-2-phenylindole-labeling MSCs were transplanted into tumor tissue in the test group (n = 10). Culture medium was injected into the tumor tissue of the control group (n = 10). The maximum diameter of the tumor mass was measured by ultrasound at 2 and 4 weeks after the VX2 tumor mass was embedded. All animals were sacrificed at 4 weeks. The double labeling immunofluorescence for CD146 was performed to reveal whether engrafted cells can differentiate into vascular endothelial cells. Vascular density was compared between the 2 groups.
There was no significant difference in the maximum diameters of the tumor masses between the 2 groups at 2 weeks (test group 0.77 +/- 0.15 cm vs. control group 0.71 +/- 0.15 cm, p > 0.05). The maximum diameters appeared larger in the test group at 4 weeks (test group 3.82 +/- 0.94 cm vs. control group 2.28 +/- 0.54 cm, p < 0.05). Immunofluorescence studies revealed some engrafted MSCs expressing a vascular endothelial cell phenotype (CD146). Furthermore, vascular density was augmented in the test group in comparison to the control group (10.1 +/- 0.70/0.2 mm(2) vs. 8.24 +/- 0.81/0.2 mm(2), p < 0.05).
Engrafted MSCs can differentiate into vascular endothelial cells and contribute to angiogenesis in the tumor microenvironment, which may be the major pathway of promoting tumor growth.
研究间充质干细胞（MSCs）在肿瘤发展过程中的作用以及MSCs在肿瘤微环境中分化为血管内皮细胞的可能性。
将20只雄性新西兰兔随机分为2组：试验组和对照组。通过骨髓细胞贴壁法分离培养MSCs。对所有兔子（n = 20），通过将VX2肿块植入膨胀的膀胱黏膜构建膀胱肿瘤模型。1周后，将4',6-二脒基-2-苯基吲哚标记的MSCs移植到试验组（n = 10）的肿瘤组织中。向对照组（n = 10）的肿瘤组织中注射培养基。在植入VX2肿瘤肿块后2周和4周，通过超声测量肿瘤肿块的最大直径。所有动物在4周时处死。进行CD146的双重标记免疫荧光以揭示植入细胞是否能分化为血管内皮细胞。比较两组之间的血管密度。
2周时两组肿瘤肿块的最大直径无显著差异（试验组0.77±0.15 cm vs.对照组0.71±0.15 cm，p>0.05）。4周时试验组的最大直径更大（试验组3.82±0.94 cm vs.对照组2.28±0.54 cm，p<0.05）。免疫荧光研究显示一些植入的MSCs表达血管内皮细胞表型（CD146）。此外，试验组的血管密度高于对照组（10.1±0.70/0.2 mm² vs. 8.24±0.81/0.2 mm²，p<0.05）。
植入的MSCs可分化为血管内皮细胞并促进肿瘤微环境中的血管生成，这可能是促进肿瘤生长的主要途径。
