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2022, Vol. 26 ›› Issue (7): 1012-1019Immunomodulatory effects of deferoxamine and interferon gamma on human dental pulp stem cellsZhou Ying1, Zhang Huan2, Liao Song3, Hu Fanqi3, Yi Jing1, Liu Yubin1, Jin Jide1
Abstract: BACKGROUND: Immune rejection is a great challenge for tissue or organ transplantation, and immunosuppressors often bring serious side effects to patients. The immunosuppressive effect of mesenchymal stem cells brings new hope for the treatment of immune rejection. OBJECTIVE: To explore the effect of combined action of deferoxamine and interferon-γ on the immunomodulatory ability of human dental pulp stem cells. METHODS: After pretreatment of human dental pulp stem cells with deferoxamine or interferon-γ or their combination, the proliferation of cells was detected with cell counting kit-8. The mRNA expression of some gene mRNA was examined by Q-PCR. The secretion of some immune regulatory factors was determined using ELISA. Thereafter, pretreated human dental pulp stem cells were co-cultured with mouse spleen lymphocytes, and then the proliferation of lymphocytes was detected by CFSE labeling by flow cytometry. After allogenic skin transplantation, mice were injected with PBS, human dental pulp stem cells or pretreated human dental pulp stem cells into tail vein immediately. The survival time of skin grafts was recorded. The pathology and immunohistochemistry of skin grafts were examined. Moreover, the proportion of Treg cells in spleen of transplanted mice was measured. RESULTS AND CONCLUSION: (1) Deferoxamine or interferon-γ pretreatment inhibited the growth of human dental pulp stem cells, and the inhibition of deferoxamine was more significant than interferon-γ. (2) Pretreatment of deferoxamine combined with interferon-γ significantly increased the gene expression of vascular endothelial growth factor, interleukin 6, transforming growth factor β1, cyclooxygenase 2, human leukocyte antigen G, tumor necrosis factor A inducible protein 6 and interleukin 10, and promote secretion of interleukin 6, transforming growth factor β1 and prostaglandin E2. (3) The results of in vivo experiments confirmed that human dental pulp stem cells pretreated with deferoxamine combined with interferon-γ prolonged the survival time of mouse allograft skin, reduced the infiltration of CD4+T, CD8+T and macrophages at the grafted skin, and increased the proportion of Treg cells in the spleen of recipient mice. (4) It is concluded that deferoxamine combined with interferon-γ pretreatment enhanced the immunomodulatory effect of human dental pulp stem cells, and inhibited the immune rejection of skin allografts. Key words:stem cells, human dental pulp stem cells, deferoxamine, interferon-γ, skin transplantation, immunomodulation, immune rejection |