RESEARCH ARTICLE


The Secretome of Mesenchymal Stem Cells Prevents Islet Beta Cell Apoptosis via an IL-10-Dependent Mechanism



Buthainah Al-Azzawi1, 3, Declan H. McGuigan2, Fiona N. Manderson Koivula2, Ajile Elttayef1, 3, Tina P. Dale1, Ying Yang1, Catriona Kelly2, Nicholas R. Forsyth1, *
1 School of Pharmacy and Bioengineering, Keele University, Keele, UK
2 Northern Ireland Centre for Stratified Medicine, School of Biomedical Sciences, Ulster University, Northern Ireland, UK
3 Biochemistry Department, College of Medicine, University of Al-Qadisiyah, Al Diwaniyah, Iraq

Article Information


Identifiers and Pagination:

Year: 2020
Volume: 6
First Page: 1
Last Page: 12
Publisher Id: TOSCJ-6-1
DOI: 10.2174/1876893802006010001

Article History:

Received Date: 30/12/2019
Revision Received Date: 20/01/2020
Acceptance Date: 09/02/2020
Electronic publication date: 20/03/2020
Collection year: 2020

© 2020 Al-Azzawi et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Thornburrow Drive, Stoke-on-Trent, ST4 7QB, Keele, UK, Tel: +44 (0)1782 674388;
Email: n.r.forsyth@keele.ac.uk


Abstract

Background:

Type 1 Diabetes Mellitus (T1DM) is partly driven by autoimmune destruction of the pancreatic beta cell, facilitated by the release of inflammatory cytokines, including IFN-γ, TNF-α and IL-1β by cells of the innate immune system. Mesenchymal Stem Cells (MSCs) have been used to counteract autoimmunity in a range of therapeutic settings due to their secretion of trophic and immunomodulatory factors that ameliorate disease independently of the cells themselves.

Objective:

The aim of this study was to assess the effect of the secretome of human bone-marrow derived MSCs on cytokine-driven beta cell apoptosis.

Methods:

All experiments were conducted in two insulin-secreting islet cell lines (BRIN-BD11 and βTC1.6) with selected experiments confirmed in primary islets. MSC secretome was generated by conditioning serum-free media (MSC-CM) for 24 hours on sub-confluent MSC populations. The media was then removed and filtered in readiness for use.

Results:

Exposure to IFN-γ, TNF-α and IL-1β induced apoptosis in cell lines and primary islets. The addition of MSC-CM to cell lines and primary islets partially reversed cytokine-driven apoptosis. MSC-CM also restored glucose-stimulated insulin secretion in cytokine-treated cell lines, which was linked to improved cell viability following from cytokine challenge. Characterization of MSC-CM revealed significant concentrations of IL-4, IL-10, PIGF and VEGF. Of these, IL-10 alone prevented cytokine-driven apoptosis. Furthermore, the inhibition of IL-10 through the addition of a blocking antibody reversed the anti-apoptotic effects of MSC-CM.

Conclusion:

Overall, the protective effects of MSC-CM on islet beta cell survival appear to be largely IL-10-dependent.

Keywords: Apoptosis, Beta-cell, Islet, IL-10, MSCs, Mesenchymal Stromal Cells, Mesenchymal Stem Cells, Secretome.