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


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.


CONCLUSIONS
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.
Kang
Seok-Gu
SG
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.
Jeun
Sin Soo
SS
Lim
Jung Yeon
JY
Kim
Seong Muk
SM
Yang
Yoon Sun
YS
Oh
Won Il
WI
Huh
Pil-Woo
PW
Park
Chun Kun
CK
D001932:Brain Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D053686:Fetal Stem Cells / Q000166:cytology / Q000276:immunology*; D005910:Glioma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014470:Umbilical Cord
D007375:Interleukin-1; D019409:Interleukin-15; D016178:Granulocyte-Macrophage Colony-Stimulating Factor