Keele Research Repository

Type 1 diabetes is a challenging condition to manage effectively. Utilising the mesenchymal stem cell (MSC) secretome is an avenue being researched in regenerative medicine which could potentially ameliorate the condition. Previous studies have identified potential anti-apoptotic, trophic and immunomodulatory factors that may be implicated in its therapeutic effect.
We theorise that ILZ10 may play an important role in disease modulation. This study aims to explore the effects of MSC-conditioned medium (MSCZ-CM) on in vitro and in vivo models of diabetes as well as to characterise the presence of ILZ10 receptors on beta cell lines.
BRIN-bd11 and TC6 cells were exposed to increasing concentrations of pro-inflammatory cytokines (TNFα, IFNγ, ILZ1β) implicated in the pathogenesis of type 1 diabetes for 24 hours, both in the presence and absence of MSC-CM. MTT assays were used to determine falls in viability. To determine the effect of MSC-CM on an in vivo model of diabetes, diabetes was induced in mice via intraperitoneal injections of STZ. Mice treated with Intraperitoneal MSC-CM were compared to untreated diabetic mice and a non-diabetic control. A plasma insulin ELISA, DEXA scans and pancreatic histology were used for analysis. Characterisation of IL-10 on BRIN-bd11 and TC6 cells was performed using electrophoresis and immunofluorescence techniques.
This thesis demonstrates that the MSC-CM ameliorates falls in viability of BRIN-bd11 and TC6 cell lines in the presence of pro-inflammatory cytokines implicated in the pathogenesis of diabetes in an in vitro model. It also demonstrates that MSC-CM potentially improves the histology and biochemistry of diabetic mice in vivo. We also demonstrated the presence of IL-10 receptors on beta cell lines.
Thus, MSC-CM appears to be a potential therapeutic tool for use in type 1 diabetes. Further research needs to be conducted to determine the mechanisms through which paracrine factors including IL-10 exert their therapeutic effect.