Skip to main content

Research Repository

Advanced Search

THERAPEUTIC EFFECTS OF HYPOXIC AND PRO-INFLAMMATORY PRIMING OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN INFLAMMATORY ARTHRITIS

Kay, Alasdair G.; Treadwell, Kane; Roach, Paul; Morgan, Rebecca; Lodge, Rhys; Hyland, Mairead; Piccinini, Anna M.; Forsyth, Nicholas R.; Kehoe, Oksana

THERAPEUTIC EFFECTS OF HYPOXIC AND PRO-INFLAMMATORY PRIMING OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN INFLAMMATORY ARTHRITIS Thumbnail


Authors

Alasdair G. Kay

Kane Treadwell

Paul Roach

Rebecca Morgan

Rhys Lodge

Mairead Hyland

Anna M. Piccinini

Nicholas R. Forsyth



Abstract

<jats:title>Abstract</jats:title><jats:p>Novel biological therapies have revolutionised the management of Rheumatoid Arthritis (RA) but no cure currently exists. Mesenchymal stem cells (MSCs) immunomodulate inflammatory responses through paracrine signalling, including via secretion of extracellular vesicles (EVs) in the cell secretome. We evaluated the therapeutic potential of MSCs-derived small EVs in an antigen-induced model of arthritis (AIA).</jats:p><jats:p>EVs isolated from MSCs cultured normoxically (21% O<jats:sub>2</jats:sub>, 5% CO<jats:sub>2</jats:sub>), hypoxically (2% O<jats:sub>2</jats:sub>, 5% CO<jats:sub>2</jats:sub>) or with a pro-inflammatory cytokine cocktail were applied into the AIA model. Disease pathology was assessed post-arthritis induction through swelling and histopathological analysis of synovial joint structure. Activated CD4+ T cells from healthy mice were cultured with EVs or MSCs to assess deactivation capabilities prior to application of standard EVs <jats:italic>in vivo</jats:italic> to assess T cell polarisation within the immune response to AIA.</jats:p><jats:p>All EVs treatments reduced knee-joint swelling whilst only normoxic and pro-inflammatory primed EVs improved histopathological outcomes. In vitro culture with EVs did not achieve T cell deactivation. Polarisation towards CD4+ helper cells expressing IL17a (Th17) was reduced when normoxic and hypoxic EV treatments were applied in vitro. Normoxic EVs applied into the AIA model reduced Th17 polarisation and improved Th17:Treg homeostatic balance.</jats:p><jats:p>Priming of MSCs in EV production can be applied to alter the therapeutic efficacy however normoxic EVs present the optimal strategy for broad therapeutic benefit. The varied outcomes observed in MSCs priming may promote EVs optimised for therapies targeted for specific therapeutic priorities. EVs present an effective novel technology with potential for cell-free therapeutic translation.</jats:p>

Journal Article Type Article
Acceptance Date Dec 20, 2021
Online Publication Date Dec 23, 2021
Publicly Available Date May 30, 2023
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Electronic ISSN 1422-0067
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 23
Issue 1
Article Number 126
DOI https://doi.org/10.3390/ijms23010126
Related Public URLs https://www.biorxiv.org/content/10.1101/2021.06.28.450178v2

Files







You might also like



Downloadable Citations