Malignant transformation of human umbilical mesenchymal stem cells induced by 3-methycholanthrene

Abstract

Objective To confirm the possible malignant transformation of human umbilical mesenchymal stem cells (HUMSCs) induced by 3-methycholanthrene (MCA), to seek for a noval mode that can evaluate the security of its clincial application and explore effective methods to prevent HUMSCs from malignant transformation. Methods Primary HUMSCs was isolated and expanded by tissue adherent culture. The test group was treated with MCA in culture medium for a week. Then the medium was changed twice weekly. The control group was cultured in medium containing dimethyl sulphoxide. Then 2 groups were tested for malignancy by the observations of morphological change and proliferation data on an inverted microscope. Transformed cells were injected subcutaneously into immune-deficient mice. Tumor tissue sections were analyzed by histology and immunochemistry to identify tumor types, and karotype analysis was taken to comfirm whether the cells come form humanbeing. Results Nine dornors of HUMSCs which propagated in culture continuously for up to 30-60 days ultimately undergo senescence. Whereas 1 in 9 dornors of HUMSCs treated with MCA can bypass senescence and undergo malignant transformation which gave rise to sarcoma or poor differentiated tumor analysised by HE staining and immunohistochemical staining. Karotype analysis confirmed the human cell origin of the tumor. Conclusions HUMSCs which treated with MCA can lead to malignant transformation. It might also represent a potential source of malignancy in vivo. Because of malignant possibility of HUMSCs, its security of clinical application is still need to be verified. Key words: Human umbilical mesenchymal stem cell; Malignant transformation; 3-methycholanthrene