[Study of mesenchymal stem cells transfected with oncogenes differentiate into hepatocellular carcinoma of rats].
OBJECTIVE
To investigate the effect of rat mesenchymal stem cells (MSCs) transfected with different oncogenes differentiate into hepatocellular carcinoma (HCC) in vitro.


METHODS
MSCs, transfected with different oncogenes c-myc, K-ras, c-myc and K-ras and amplified in vitro, were infused into rats via vena portae. The recipient rats were divided into the hepatic impairment group, which were fed with tetrachloromethane and the healthy control group. At day 7, 14, 21, 28 and 42 following grafting, the complete livers were obtained and examined using fluorescence detection, conventional pathology and immunohistochemistry detection of GFP, c-kit and AFP to study the colonization and distribution of stem cells in rat liver.


RESULTS
No immunological rejection occurred after grafting of allogenic MSCs. The infused MSCs colonized in the recipient rat liver. Liver tumors were present in 6 rats grafted with MSCs that were transfected with K-ras, K-ras and c-myc, and the protein expression of AFP was detected using immunocytochemistry at day 7. Rats grafted with MSCs that were transfected with c-myc gene had no obvious tuberosity or tumor. Small oval cells were found microscopically in the periphery of vena portae, and immunohistochemistry staining of AFP was negative. Immunohistochemical staining of c-kit was positive in all livers of rats that were transfected with MSCs.


CONCLUSIONS
Hepatocellular carcinoma may derive from genetically mutated MSCs.
Zhang
Gang-qing
GQ
Department of General Surgery, the Second People's Hospital of Guangdong Province, Guangzhou 510317, China.
Fang
Chi-hua
CH
Gao
Peng
P
Yan
Zheng
Z
Zheng
Quan
Q
Chen
Gui-hua
GH
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
D049452:Green Fluorescent Proteins