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Cytotoxicity of human umbilical cord blood-derived mesenchymal stem cells against human malignant glioma cells.

Kang SG, Jeun SS, Lim JY, Kim SM, Yang YS, Oh WI, Huh PW, Park CK

Department of Neurosurgery, The Catholic University of Korea College of Medicine, Uijeongbu St. Mary’s Hospital, 65-1, Kumoh-dong, Uijeongbu, 480-130, South Korea.

BACKGROUND: Mesenchymal stem cells (MSCs) represent a potential useful source for cell-based glioma therapies because these cells evidence both orthodox and unorthodox plasticity and also show tropism for cancer. In this study, the authors attempted to access the cytotoxicity of human umbilical cord blood (hUCB)-derived MSCs, with or without cytokine activations against malignant glioma cells. MATERIALS AND METHODS: hUCB-derived MSCs were activated by interleukin-2, interleukin-15, granulocyte macrophage colony-stimulating factor, and combinations. The hUCB-derived MSCs and activated hUCB-derived MSCs were effector cells. The cytotoxicity of the unactivated hUCB-derived MSCs and activated hUCB-derived MSCs against the target cells (human malignant glioma cells) was estimated via visual survival cell assays and transwell inserts. Phenotypic changes occurring in these hUCB-derived MSCs before and after cytokine activation were determined via flow cytometry. The secreted proteins from these effector cells were estimated via enzyme-linked immunosorbent assays. RESULTS: We noted a significant cytotoxicity of hUCB-derived MSCs against malignant glioma cells. In addition, the hUCB-derived MSCs activated with cytokines evidenced significantly higher cytotoxicity than that observed with unactivated hUCB-derived MSCs. Differentiated immune effectors cells from the hUCB-derived MSCs after cytokine activation were not shown to have increased in number. However, the activated hUCB-derived MSCs secreted more immune response-related proteins (interleukin 4, interferon-gamma) than did the unactivated hUCB-derived MSCs. CONCLUSION: The data collected herein confirm for the first time that hUCB-derived MSCs, with or without activation, evidence significant cytotoxicity against human malignant glioma cells, and the immune response-related proteins secreted in this process may perform relevant functions.

Published 4 February 2008 in Childs Nerv Syst, 24(3): 293-302.
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