Objects: Marrow stromal cells (MSCs) have been shown to have the capacity of orthodox and unorthodox plasticity. In this study, the authors tried to access in vitro cytotoxicity of MSCs from rat and also to differentiate MSCs into immune effector cell. Methods: Rat MSCs (rMSCs) were isolated by standard methodology and were activated by interleukin-2 (IL-2), interleukin-15 (IL-15), granulocyte macrophage colony stimulating factor, and combinations, which were effector cells. Cytotoxicity of rMSCs and activated rMSCs against the target cells (9L rat glioma cell line) was estimated using visual survival cell assay. Phenotypes of these various activated cells were determined using flow cytometry. The secreted protein from effector cells was estimated by enzyme-linked immunosorbent assay. The expression of immune response-related genes in activated cells was measured. Results: There was a significant cytotoxicity of rMSCs activated with various cytokine combinations. After various cytokine activations of rMSCs, the population of immune effector cells (CD8, CD161a) and immune reaction-related proteins (IL-4, γ-INF) might increase. Apoptosis may be one of the lysis mechanisms of target cells by activated rMSCs. The contributing genes could be γ-INF, FasL, and perforin. Conclusion: This study suggests that rMSC may be used as adoptive transfer therapy in patients suffering from malignant brain tumor, but we have to investigate orthotopic animal study for the proper translation.
Bibliographical noteFunding Information:
Acknowledgements This study was supported by a grant of the High-performance Cell Therapy R&D Center, Ministry of Health and Welfare, Republic of Korea. We are grateful to Chung Hun Rhy, M. S., for his help with the visual survival cell assay, Sun Woo Kim, for her expert advice in the statistical work of this study, and also Hyun Jeong Lim and Hee Jin Bae for editing the manuscript.
All Science Journal Classification (ASJC) codes
- Pediatrics, Perinatology, and Child Health
- Clinical Neurology