[Effect of bone marrow mesenchymal stem cells on tumor neovascularization].
OBJECTIVE
The effect of human bone marrow mesenchymal stem cells (hMSCs) on tumor neovascularization were studied.


METHODS
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.


RESULTS
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.


CONCLUSIONS
MSCs have the effect of promoting tumor neovascularization.
The Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.
Xu
X
He
Xin-rui
XR
Wang
Xu-fang
XF
Yang
Li-hong
LH
Zhang
Yun
Y
Niu
Yu-lin
YL
Li
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology