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• W3136315080 endingPage "101085" @default.
• W3136315080 startingPage "101085" @default.
• W3136315080 abstract "Allogeneic fibroblasts containing-dermal substitutes are known as neutral allografts. There is evidence that successive subculturing of fibroblasts leads to a decrease in HLA class I expression. The aim of this study was to investigate this downregulation and its correlation with the expression of interferon-beta (IFN- β) as a HLA class I regulating cytokine. This correlation was also measured under serum starvation that is prevalent in wounds, especially in burn wounds, and that is also used in pre-transplantation fibroblasts culture to manufacture bioengineered skin substitutes on an industrial scale. Fibroblasts isolated from neonatal foreskin were cultured for eight successive passages in DMEM supplemented with bovine serum (n = 3). Those cells were also cultured for different time points in DMEM without serum (n = 4). Flow cytometry, Elisa, and real-time PCR methods were used to determine the levels of HLA class I expression, IFN-β protein and IFN-β mRNA respectively. The expression of HLA class I molecules was not significantly altered by cell subculturing (p > 0.05). Interestingly, these cells also produced substantial levels of IFN-β -mRNA and -protein with non-significant alterations upon successive sub-culturing (p > 0.05). However, HLA expression in starved fibroblasts was significantly raised in a timely-dependent manner (r2 = 0.84, p < 0.001), with strong correlation with IFN-β concentrations (r2 = 0.86, p < 0.0001). These data reveal that sub-cultured allogeneic fibroblasts are not HLA negative cells supported by cells spontaneous production of IFN-β, a multifunctional immunoregulatory cytokine. Even the levels of this antigen can be increased in association with IFN-β up-regulation in certain stressful conditions, such as growth factor deprivation. These findings open a new window in transplantation immunology for immuneregulatory roles of metabolic stress- IFN-β-HLA axis leading to successful allogeneic HLA-unmatched organ transplantation in immunocompetence recipients. Moreover these data can be applied in the optimization of conditions for pre-clinical fibroblasts culture to the better designation of human dermal substitutes." @default.
• W3136315080 created "2021-03-29" @default.
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• W3136315080 date "2021-06-01" @default.
• W3136315080 modified "2023-10-07" @default.
• W3136315080 title "No mitigation of IFN-β and HLA class I expression in early sub-cultured human neonatal skin fibroblasts but both molecules are overexpressed in starved cells" @default.
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• W3136315080 doi "https://doi.org/10.1016/j.genrep.2021.101085" @default.
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