Tumorigenesis of bone marrow stromal cells transplanted into the brain of Sprague-Dawley rats: Report of three cases / 肿瘤

ABSTRACT

Objective: To investigate the possible oncogenicity of bone marrow stromal stem cells (BMSCs) transplanted into brain and its underlying mechanism. Methods: The contralateral hemiplegia became gradually worse in three Sprague-Dawley rats among twenty rats after intracerebral transplantation with BMSCs. The intracerebral space occupying lesions were examined by MRI, and the life span of these rats was observed and recorded. The tumor tissues were obtained after the three rats were sacrificed. The telomerase activity was detected by telemeric repeat amplification protocol (TRAP)- PCR-enzyme-linked immunosorbent assay (ELISA). The expressions of proliferating cell nuclear antigen (PCNA), nestin and glial fibrillary acidic protein (GFAP) were detected by immunohistochemistry. The relative expression levels of epidermal growth factor receptor(EGFR), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) proteins in intracerebral tumor tissues and normal tissues were examined by Western blotting. Results: Of twenty rats, three rats displayed left hemiplegia which was continuously getting worse, and the life spans of the three rats were 129, 174 and 187 d, respectively. The result of TRAP-PCR-ELISA showed that the telomerase activity of intracerebral tumor tissues was higher than that of intracerebral normal tissues. The expressions of PCNA and nestin proteins in intracerebral tumor tissues were both higher but the expression of GFAP was lower than those of intracerebral normal tissues. The results of Western blotting showed that among three rats with intracerebral normal tissues, the expression level of EGFR protein was increased in one rat while the expression level of VEGF protein was increased in two rats. There was no significant difference in the expression of MMP-9 protein among the three rats. Conclusion: The telomerase activity and the ability of cell proliferation of BMSCs can be enhanced and the activation of oncogenes can be observed after long-term cell culture in vitro, and these findings suggest that the tumorigenesis potential can be induced after intracerebral transplantation with MSCs. Copyright© 2011 by TUMOR.