Bone marrow mesenchymal stem cells induce angiogenesis and promote bladder cancer growth in a rabbit model.

ABSTRACT

OBJECTIVES: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.