[Effects of mesenchymal stem cell transplantation on growth of liver cancer: experiment with rats].
OBJECTIVE
To evaluate the effects of mesenchymal stem cell (MSC) transplantation on the growth of liver cancer.


METHODS
MSCs were isolated from the bone marrows of SD rats. Walker-256 cancer cells were isolated from the cancerous ascites of rat and cultured. Forty-five SD rats were randomly divided into 3 equal groups: mixed transplantation group undergoing laparotomy and transplantation of cancer cells mixed with MSCs into the liver, MSC IV transplantation group undergoing injection of MSCs into the caudal vein, and control group undergoing only MSC transplantation into the liver. MR imaging was performed s at days 3, 6, 9 and 12 after modeling to measure the maximum cross section area of the tumor. At day 12 the rats were killed after MR imaging with their livers taken out to undergo HE staining and pathological examination. Immunohistochemistry was used to detect the expression of vascular endothelial cell growth factors (VEGF), nm23 gene, a tumor metastasis inhibiting gene, and proliferating cell nuclear antigen (PCNA), a nuclear polypeptide necessary in the DNA synthesis.


RESULTS
No significant evidence of tumor formation was detected by MRI at days 3 and 6 after modeling in all rats and tumor nodules were observed since day 9. The maximum cross section areas of tumor of the mixed transplantation group and MSC IV transplantation group were significantly larger than that of the control group at days 9 and 12 (F = 4.21, P < 0.05; F = 8.52, P < 0.01). Immunohistochemistry showed that VEGF expression levels of the two study groups were both significantly higher than that of the control group (F = 9.58, P < 0.01), while the nm23 gene expression levels of the 2 study groups were both significantly lower than that of the control group (F = 4.61, P < 0.05). The PCNA expression level of the mixed transplantation group was significantly higher than that of the control group (d'((1, 0.05)) = 0.34, d'((1, 0.01)) = 0.63, P < 0.05), however, there was no significant difference in the PCNA expression level between the MSCs IV transplantation group and the control group (d'((1, 0.05)) = 0.32, d'((1, 0.01)) = 0.48, P > 0.05). There was no significant difference in the tumor apoptotic index between the 2 study groups and the control group (F = 1.25, P > 0.05).


CONCLUSIONS
MSC transplantation increases the expression of VEGF and PCNA, while decreases the expression of nm23 gene in cancer cells, thus favoring the tumor growth.
Shao
Zhi-Hong
ZH
Department of Radiology, Tongji Hospital of Tongji University, Shanghai 200065, China.
Wang
Pei-Jun
PJ
Li
Ming-Hua
MH
Zhang
Wei
W
Zheng
Shao-Qiang
SQ
Zhao
Xiao-Hu
XH
Wang
Guo-Liang
GL
Shang
Ming-Yi
MY
Mao
Xin-Qing
XQ
D000818:Animals; D002279:Carcinoma 256, Walker / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology* / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D054778:NM23 Nucleoside Diphosphate Kinases; D018809:Proliferating Cell Nuclear Antigen; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat