The novel human EndoC-βH5 cells as a valid model to study cytokine-mediated β-cell destruction

Introduction: The novel insulin producing β-cell model, EndoC-βH5, has recently become commercially available for the scientific community. The cells promise valuable prospects as a missing link in the study of primary human β cells and diabetes. Pro-inflammatory cytokines are known mediators of β-cell destruction in type 1 diabetes (T1D), therefore characterization of the cells’ cytokine sensitivity is warranted for the purpose of establishing their use as a model to study T1D. Here, we aimed to characterize the sensitivity profile of EndoC-βH5 cells to cytokines, to validate the cells as a new potential system to study β-cell loss and dysfunction in T1D.
Material and methods: EndoC-βH5 cells were exposed to the pro-inflammatory cytokines IL-1β, IFNγ and TNF-α to model T1D, in titration and time-course experiments. Cell survival and apoptosis responses were evaluated using the ApoTox-Glo Triplex Assay and Western Blotting. Glucose-stimulated insulin secretion (GSIS) and cellular insulin content were used to evaluate β-cell function. Coding and non-coding gene expression were investigated by stranded RNA sequencing and real-time qPCR transcriptomics.
Results: We demonstrate that cytokines induce apoptosis in EndoC-βH5 cells in a time- and dose-dependent manner. IFNγ proved to be the single most pro-apoptotic cytokine. Upon cytokine exposure, several coding and non-coding RNAs were differentially expressed, including key T1D-relevant genes e.g., HLA A/B/C, the endoplasmic reticulum stress marker CHOP, and several chemokines such as CXCL10. Furthermore, cytokine exposure caused diminished GSIS and cellular insulin content.
Conclusions: Our findings suggest that EndoC-βH5 cells hold promise as a valid new human model to study cytokine-induced β-cell destruction, allowing the investigation of in-debt cellular pathways and molecular mechanisms implicated in T1D.