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

Buthainah Al-Azzawi, Declan Mc Guigan, Fiona Manderson Koivula, Ajile Elttayef, Tina Dale, Ying Yang, Catriona Kelly, Nicholas Forsyth

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
29 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalThe Open Stem Cell Journal
Volume6
Issue number1
Early online date20 Mar 2020
DOIs
Publication statusPublished - 2020

Bibliographical note

Funding Information:
This work was supported by the Iraqi Ministry of Higher Education and Scientific Research (MOSHER) with grant no. S912, the European Union Regional Development Fund (ERDF) EU Sustainable Competitiveness Programme for N. Ireland; Northern Ireland Public Health Agency (HSC R&D) & Ulster University.

Publisher Copyright:
© 2020 Al-Azzawi et al.

Keywords

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

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