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 journalArticle

Abstract

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
Number of pages12
JournalThe Open Stem Cell Journal
Volume6
Early online date20 Mar 2020
DOIs
Publication statusE-pub ahead of print - 20 Mar 2020

Keywords

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

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