A study of the transformation of umbilical cord mesenchymal stem cells by interferon-gamma

Iran J Basic Med Sci. 2021 Sep;24(9):1203-1210. doi: 10.22038/ijbms.2021.56619.12639.

Abstract

Objectives: Mesenchymal stem cells (MSCs) exist in almost all tissues. Their unique nature is completed by their immunomodulatory functions, holding promise for the treatment of many diseases. An inflammatory environment precedes the immunosuppressive abilities of MSCs and this study was intended to better understand how umbilical cord MSCs (UCMSCs) react to the process of inflammation, regarding their basic characteristics and behavior when primed with the key pro-inflammatory cytokine, Interferon-γ (IFNγ).

Materials and methods: Human MSCs from the umbilical cord were isolated, expanded, and treated with IFNγ. Primed cells were analyzed to define their ability to form colonies, their morphology, differentiation potential, proliferation, and apoptosis rate.

Results: UCMSCs treated with IFNγ changed their fibroblast-like morphology and retained the expression of typical MSCs markers. IFNγ treated UCMSCs had significantly higher MFI levels regarding the expression of HLA-I (980.43 ± 556.64) and PD-L1 (598.04 ± 416.90) compared with the control cells (144.97 ± 78.5 and 122.05 ± 103.83, respectively; P<0.01). Under the influence of IFNγ, the cells had a lower population doubling time compared with the control cultures (50.345 ± 9.155 versus 61.135 ± 21.110, respectively; P<0.01) and higher numbers of colony-forming unit-fibroblasts (26.0 ± 12.2 versus 10.2 ± 8.0, respectively; P<0.05). The primed MSCs could not undergo osteogenic and adipogenic differentiation. IFNγ increased the percentage of cells in the apoptotic state on day eight (29.470 ± 6.59 versus 15.708 ± 6.190, respectively; P<0.01).

Conclusion: The properties of UCMSCs can be influenced by the pro-inflammatory cytokine IFNγ.

Keywords: Cytokine; Differentiation; Inflammation; PD-L1; Proliferation; Stem cells.