Mesenchymal stem cell derived products attenuate cytokine-induced apoptosis in pancreatic beta cells

Al Azzawi, B.; Merkhan, M. M.; Kelly, C.; Forsyth, N.

Abstract

Aims:Cytokine-driven beta cell apoptosis is central to Type 1diabetes. Mesenchymal stem cells (MSCs) are multipotent cellswith significant immunomodulatory capacity, which counteractautoimmunityand enhance islet engraftment and survival. The aimof this study was to explore the therapeutic effectiveness of MSC-derived products on cytokine-induced apoptosis in beta cells and toexplore the potential mechanism of action.Methods:Human bone marrow MSCs were isolated and char-acterised as described (Samadet al. 2014,J Stem Cell Res) andconditioned media (CM) generated with and without serum over24 h in culture. A CM secretome screen was performed to identifyhighly expressed MSC-derived products. BRIN-BD11, betaTC6and primary islets (CD-1 mice) were exposed to IL-1b(10 ng/ml),TNF-a(100 ng/ml) and IFN-c(100 ng/ml) for 24 h in thepresence/absence of CM, or recombinant cytokines/growth factorsidentified through the secretome screen. The resulting effects onglucose-induced insulin secretion and content (ELISA) and apop-tosis (TUNEL) were assessed.Results:Cytokine treatment significantly (p<0.05–0.001)induced apoptosis over 24 h, which was attenuated through theaddition of serum-containing (S) or serum-free (SF) CM (p<0.01).SF-CM reduced sensitivity to TNF-ain particular (p<0.001).Consistently, cytokine-mediated reductions in glucose-inducedinsulin secretion were abolished following exposure to CM. How-ever, insulin content was not altered suggesting that this effect isattributable to enhancements in viability after CM treatment. Asecretome screen of MSC-CM revealed that IL-10 was highlyexpressed, which independently protected against cytokine-drivenbeta cell apoptosis at concentrations of 1 ng/ml (p<0.01).Conclusion:MSC-CM abrogates cytokine-induced beta cellapoptosis in cell lines and primary islets.Reference:Sohel Samad, Khondoker M Akram, Nicholas RForsyth and Monica. (2014). A SpiteriJ Stem Cells Res, Rev &Rep.1(3): 1015.ª2016 The Authors, presented at the Diabetes UK Professional Conferenceª2016 Diabetes UK.

Citation

Al Azzawi, B., Merkhan, M. M., Kelly, C., & Forsyth, N. (2016, March). Mesenchymal stem cell derived products attenuate cytokine-induced apoptosis in pancreatic beta cells. Poster presented at Abstracts of the Diabetes UK Professional Conference 2016, Scottish Exhibition and Conference Centre, Glasgow, Scotland

• Presentation Conference Type: Poster
• Conference Name: Abstracts of the Diabetes UK Professional Conference 2016
• Conference Location: Scottish Exhibition and Conference Centre, Glasgow, Scotland
• Start Date: Mar 2, 2016
• End Date: Mar 4, 2016
• Deposit Date: Jun 12, 2023
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/dme.2_13048