ORTHOPAEDIC
INSTITUTE RESEARCH

Rheumatology

Members of the Research Team:
Dr Oksana Kehoe (Lead) and PhD students Rebecca Davies, Anais Makos and Henry Barrett

Clinical Support:
Dr Ayman Askari (Lead), Dr Roshan Amarasena, Dr Julia Flint and Dr Rameez Arif.

Our team has continued to be active this year carrying out basic science work into understanding mechanisms of inflammatory arthritis diagnosis, progression and possible treatments including mesenchymal stem cells, regulatory T cells and their extracellular vesicles. We also try to find out how stem cells can be “encouraged” to perform better in aging and in disease such as arthritis.

We are very fortunate in RJAH to be able to work closely with clinicians who themselves are very interested in research.

We have been publishing our findings in the International Journal of Molecular Sciences, Inflammopharmacology, Cytotherapy and Annals of the Rheumatic Diseases and have presented our work at several national and international meetings such as the 8th Malaysian Tissue Engineering and Regenerative Medicine Scientific Meeting, March 2022; the International Society for Extracellular Vesicles Annual Meeting, May 2022, Lyon, France (Figure 1); TERMIS EU 2023, March 2023, Manchester, UK; the International Society for Extracellular Vesicles Annual Meeting, May 2023, Seattle, USA; EULAR 2023 Congress, May 2023, Milan, Italy.

We are very grateful to the Orthopaedic Institute Charity, Oswestry for their continuous support.

Figure 1 – Dr Oksana Kehoe and Rebecca Davies at the ISEV Annual Meeting in Lyon, France, May 2022.

Rheumatology Projects

THE POTENTIAL UTILITY OF HUMAN REGULATORY T CELL DERIVED EXTRACELLULAR VESICLES TO CONTROL INFLAMMATION IN RHEUMATOID ARTHRITIS (VERSUS)

Henry Barrett, Lesley Smyth†, Charlotte Hulme, Marcelo Andrade De Lima, Aled
Clayton*, Roshan Amarasena and Oksana Kehoe

†University of East London, *Cardiff University

Funded by the Orthopaedic Institute and Keele University

INVESTIGATING THE POTENTIAL OF T CELLS ISOLATED FROM JUVENILE THYMUSES FOR THE DEVELOPMENT OF ALLOGENEIC THERAPIES FOR AUTOIMMUNE CONDITIONS (SELECT)

Anais Makos, Lesley Smyth, Aled Clayton#, Rafael R Guerrero*, Dan Hawcutt*, Oksana Kehoe

University of East London, #Cardiff University ; *Alder Hey Children’s Hospital, Liverpool

Funded by the Orthopaedic Institute

SCALING UP MESENCHYMAL STROMAL CELL EXTRACELLULAR VESICLE PRODUCTION FOR THERAPEUTIC APPLICATION IN RHEUMATOID ARTHRITIS

Rebecca Davies, Claire Mennan, Karina Wright, Charlotte Hulme, Mark Platt†, Oksana Kehoe

†Loughborough University

Funded by the Orthopaedic Institute James Richardson Studentship, Keele University and EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine

PARIS STUDY: PSORIATIC ARTHRITIS – RESISTANCE TO TNF INHIBITORS STUDY

Anaïs Makos, Jan Herman Kuiper, Roshan Amarasena, Oksana Kehoe

Funded by RJAH Hospital Charitable Fund

Syndecan-3 regulates MSC adhesion, ERK and AKT signaling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo (Preclinical studies)

Fiona K Jones†, Andrei Stefan, Alasdair G Kay, Mairead Hyland, Rebecca Morgan, Nicholas R Forsyth, Addolorata Pisconti† and Oksana Kehoe

†Stony Brook University, NY, USA

Funded by Keele University School of Medicine, Oswestry Rheumatology Association and Orthopaedic Institute

Exploring the anti-inflammatory potential of extracellular vesicles from umbilical cord mesenchymal stem cells

Mairead Hyland, Claire Mennan, Daniel Tonge†, Emma Wilson#, Aled Clayton*, Oksana Kehoe

Keele University, #University of Chester; *Cardiff University

Funded by the RJAH Orthopaedic Hospital Charity, Keele ACORN and Orthopaedic Institute.

Uncovering the role of proteoglycans in exosome biogenesis for improved regenerative medicine therapies

Rebecca Morgan, Cathy Merry*, Oksana Kehoe,
*University of Nottingham

Funded by EPSRC/MRC Centre for Doctoral Training in Regenerative Medicine

Mesenchymal Stem Cell-Derived Extracellular Vesicles as Therapeutic Agents for Rheumatoid Arthritis

Mairead Hyland, Claire Mennan, Karina Wright, Roshan Amarasena*, Emma Wilson#, Aled Clayton*#, Oksana Kehoe
* RJAH Orthopaedic Hospital NHS Foundation Trust; #University of Chester; *#Cardiff University

Funded by the Orthopaedic Institute

Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Disease Severity in Inflammatory Arthritis

Alasdair Kay, Rebecca Morgan, Mairead Hyland, Andrei Stefan, Oksana Kehoe

Funding was provided by the Orthopaedic Institute Ltd, Oswestry Rheumatology Association and RJAH Hospital Charity

The in vitro effect of syndecan-3 gene knockout on bone marrow derived mesenchymal stem cells’ properties (Preclinical studies)

Andrei Stefan, Alasdair Kay, Nick Forsyth, Fiona Jones*, Dada Pisconti*, Oksana Kehoe
*University of Liverpool

Funded by Orthopaedic Institute, Keele University School of Medicine and Oswestry Rheumatology Association

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