Study of bone mesenchymal stem cells tropism for hepatic tumors and effect on the form of tumor stromal

Abstract

To investigate the tropism capacity of the rat bone mesenchymal stem cells (BMSC) for hepatic tumors microenvironment and the effect on the form of tumor stromal. Rat BMSC were isolated, cultured and expanded, then incubated with superparamagnetic iron oxide (SPIO) nanoparticles. Prussian blue stain was performed for showing intracellular irons. Walker-256 cells were injected into the rat livers directly to establish hepatic tumor models. The experiment was divided into two experimental groups (the group venous injected with BMSC after tumors becoming mass: tail venous injected with BMSC after MR showed the presence of tumors at 6-8 days after operation and the group venous injected with BMSC before tumors becoming mass: tail venous injected with BMSC when MR showed no presence of tumors at 3 days after operation) and one control group. To the experimental groups animals, MRI was made before venous injection of BMSC and at 5, 10, 15 days after BMSC transplantation. The rats were killed at corresponding period. The pathologic examinations were analyzed, including HE, Prussian blue stain. The expression of vascular endothelial growth factor (VEGF), CD31, von Willebrand factor (vWF) in the specimens harvested at 10 days after BMSC transplantation were detected immunohistochemically. Prussian blue staining of SPIO labeled BMSC demonstrated cells could be effectively labeled and the labeling efficiency was almost 90%. After BMSC transplantation, two experimental groups were showed tuberculous signal intensity loss at the margin of tumors on T(2) weighted MR images at 5, 10 days after transplantation and the signal intensity loss was not visualized at 15 days after transplantation. The control group was not observed signal intensity decrease. Prussian blue staining of histological analysis showed blue-stained iron particles distributed at the margin of tumor at 5, 10, 15 days after transplantation. Immunohistochemical examination showed that the expression of VEGF, CD31, vWF in two experimental groups at 10 days after transplantation were higher than that in the control group (F = 34.03, P < 0.01; F = 84.24, P < 0.01; F = 7.08, P < 0.05). Rat BMSC have the ability to migrate towards hepatic tumors in vivo and promote to form vascular endothelium.