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Extracellular vesicle bioactivity and potential clinical utility is determined by mesenchymal stromal cell clonal subtype (2024)
Journal Article
Ioannou, S., G Kay, A., P Stone, A., Rand, E., Elberfeld, S., Bolton, W., …Genever, P. (in press). Extracellular vesicle bioactivity and potential clinical utility is determined by mesenchymal stromal cell clonal subtype. bioRxiv, https://doi.org/10.1101/2024.09.05.609844

Mesenchymal stromal cells (MSCs) are a promising source of therapeutic extracellular vesicles (EVs), however it is not clear how heterogeneity within a non-clonal MSC population will affect the collective EV pool. Here we used immortalised clonal MSC... Read More about Extracellular vesicle bioactivity and potential clinical utility is determined by mesenchymal stromal cell clonal subtype.

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches (2024)
Journal Article
Kehoe, O., Welsh, J. A., Goberdhan, D. C., O'Driscoll, L., Buzas, E. I., Blenkiron, C., …Witwer, K. W. (2024). Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. Journal of Extracellular Vesicles, 13(2), Article e12404. https://doi.org/10.1002/jev2.12404

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have
generated b... Read More about Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.

ST2-Conditioned Medium Fosters Dorsal Horn Cell Excitability and Synaptic Transmission in Cultured Mouse Spinal Cord. (2023)
Journal Article
Juárez, E. H., Wood, C. R., Davies, R., Kehoe, O., Johnson, W. E., Merighi, A., & Ferrini, F. (2023). ST2-Conditioned Medium Fosters Dorsal Horn Cell Excitability and Synaptic Transmission in Cultured Mouse Spinal Cord. Stem Cell Reviews and Reports, 19, 2918-2928. https://doi.org/10.1007/s12015-023-10618-x

Conditioned medium obtained from bone marrow-derived stem cells has been proposed as a novel cell-free therapy in spinal cord injury and neuropathic pain, yet the direct effect on spinal neuron function has never been investigated. Here, we adopted s... Read More about ST2-Conditioned Medium Fosters Dorsal Horn Cell Excitability and Synaptic Transmission in Cultured Mouse Spinal Cord..

Extracellular vesicles derived from umbilical cord mesenchymal stromal cells show enhanced anti-inflammatory properties via upregulation of miRNAs after pro-inflammatory priming (2023)
Journal Article
Hyland, M., Mennan, C., Davies, R., Wilson, E., Tonge, D. P., Clayton, A., & Kehoe, O. (2023). Extracellular vesicles derived from umbilical cord mesenchymal stromal cells show enhanced anti-inflammatory properties via upregulation of miRNAs after pro-inflammatory priming. Stem Cell Reviews and Reports, 19, 2391–2406. https://doi.org/10.1007/s12015-023-10586-2

Autoimmune conditions, such as rheumatoid arthritis, are characterised by a loss of immune tolerance, whereby the immune cells attack self-antigens causing pain and inflammation. These conditions can be brought into remission using pharmaceutical tre... Read More about Extracellular vesicles derived from umbilical cord mesenchymal stromal cells show enhanced anti-inflammatory properties via upregulation of miRNAs after pro-inflammatory priming.

Extracellular Vesicle Depletion Protocols of Foetal Bovine Serum Influence Umbilical Cord Mesenchymal Stromal Cell Phenotype, Immunomodulation, and Particle Release (2023)
Journal Article
Davies, R., Allen, S., Mennan, C., Platt, M., Wright, K., & Kehoe, O. (2023). Extracellular Vesicle Depletion Protocols of Foetal Bovine Serum Influence Umbilical Cord Mesenchymal Stromal Cell Phenotype, Immunomodulation, and Particle Release. International Journal of Molecular Sciences, 24(11), 9242. https://doi.org/10.3390/ijms24119242

The immunomodulatory properties of MSCs can be recreated using their extracellular vesicles (EVs). Yet, the true capabilities of the MSC EVs cannot be distinguished from contaminating bovine EVs and protein derived from supplemental foetal bovine ser... Read More about Extracellular Vesicle Depletion Protocols of Foetal Bovine Serum Influence Umbilical Cord Mesenchymal Stromal Cell Phenotype, Immunomodulation, and Particle Release.

Psoriatic arthritis: review of potential biomarkers predicting response to TNF inhibitors (2022)
Journal Article
Makos, A., Kuiper, J., Kehoe, O., & Amarasena, R. (2022). Psoriatic arthritis: review of potential biomarkers predicting response to TNF inhibitors. Inflammopharmacology, 77-87. https://doi.org/10.1007/s10787-022-01092-x

Psoriatic arthritis (PsA) is a chronic and painful inflammatory immune-mediated disease. It affects up to 40% of people with psoriasis and it is associated with several comorbidities such as obesity, diabetes, metabolic syndrome and hypertension. PsA... Read More about Psoriatic arthritis: review of potential biomarkers predicting response to TNF inhibitors.

THERAPEUTIC EFFECTS OF HYPOXIC AND PRO-INFLAMMATORY PRIMING OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN INFLAMMATORY ARTHRITIS (2021)
Journal Article
Kay, A. G., Treadwell, K., Roach, P., Morgan, R., Lodge, R., Hyland, M., …Kehoe, O. (in press). THERAPEUTIC EFFECTS OF HYPOXIC AND PRO-INFLAMMATORY PRIMING OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN INFLAMMATORY ARTHRITIS. International Journal of Molecular Sciences, 23(1), Article 126. https://doi.org/10.3390/ijms23010126

<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 si... Read More about THERAPEUTIC EFFECTS OF HYPOXIC AND PRO-INFLAMMATORY PRIMING OF MESENCHYMAL STEM CELL-DERIVED EXTRACELLULAR VESICLES IN INFLAMMATORY ARTHRITIS.

Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Inflammatory Arthritis (2021)
Journal Article
Kay, A. G., Roach, P., Morgan, R., Lodge, R., Hyland, M., Piccinini, A. M., …Treadwell, K. (2021). Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Inflammatory Arthritis. International Journal of Molecular Sciences, 23(1), 126 - 126. https://doi.org/10.3390/ijms23010126

<jats:p>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... Read More about Therapeutic Effects of Hypoxic and Pro-Inflammatory Priming of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Inflammatory Arthritis.

Hypoxic and pro-inflammatory priming of mesenchymal stem cell-derived extracellular vesicles to reduce disease severity and immune responses in inflammatory arthritis (2021)
Presentation / Conference
Kay, A. G., Treadwell, K., Roach, P., Morgan, R., Lodge, R., Hyland, M., …Kehoe, O. (2021, September). Hypoxic and pro-inflammatory priming of mesenchymal stem cell-derived extracellular vesicles to reduce disease severity and immune responses in inflammatory arthritis. Poster presented at 6th European Congress of Immunology, Virtual meeting

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... Read More about Hypoxic and pro-inflammatory priming of mesenchymal stem cell-derived extracellular vesicles to reduce disease severity and immune responses in inflammatory arthritis.

Syndecan-3: A Signaling Conductor in the Musculoskeletal System (2021)
Book Chapter
Jones, F. K., Kehoe, O., Daroszewska, A., van’t Hof, R. J., & Pisconti, A. (2021). Syndecan-3: A Signaling Conductor in the Musculoskeletal System. In Proteoglycans in Stem Cells (153-177). Springer. https://doi.org/10.1007/978-3-030-73453-4_7

Syndecan-3 is a transmembrane proteoglycan, the largest of the four syndecan family members and the most mysterious. To date, the number of published studies involving syndecan-3 is only a small fraction of the number of studies involving the other s... Read More about Syndecan-3: A Signaling Conductor in the Musculoskeletal System.

Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo (2020)
Journal Article
Jones, F. K., Stefan, A., Kay, A. G., Hyland, M., Morgan, R., Forsyth, N. R., …Kehoe, O. (2020). Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo. Scientific reports, https://doi.org/10.1038/s41598-020-77514-z

Rheumatoid arthritis (RA) is a debilitating and painful inflammatory autoimmune disease characterised by the accumulation of leukocytes in the synovium, cartilage destruction and bone erosion. The immunomodulatory effects of bone marrow derived mesen... Read More about Syndecan-3 regulates MSC adhesion, ERK and AKT signalling in vitro and its deletion enhances MSC efficacy in a model of inflammatory arthritis in vivo.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce Disease Severity and Immune Responses in Inflammatory Arthritis (2020)
Other
Kay, A., Roach, P., Treadwell, K., Morgan, R., Lodge, R., Hyland, M., …Forsyth, N. R. (2020). Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce Disease Severity and Immune Responses in Inflammatory Arthritis

Abstract Background 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 via growth f... Read More about Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce Disease Severity and Immune Responses in Inflammatory Arthritis.

Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles (2020)
Journal Article
Kehoe, O., Hyland, M., Mennan, C., Wilson, E., & Clayton, A. (2020). Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles. Cells, https://doi.org/10.3390/cells9030726

Umbilical cord mesenchymal stromal cells (UCMSCs) have shown an ability to modulate the immune system through the secretion of paracrine mediators, such as extracellular vesicles (EVs). However, the culture conditions that UCMSCs are grown in can alt... Read More about Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles.

Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis (2019)
Journal Article
Eustace, A., McNaughton, E., King, S., Kehoe, O., Kungl, A., Mattey, D., …Middleton, J. (2019). Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis. Arthritis Research and Therapy, 21, Article 172. https://doi.org/10.1186/s13075-019-1939-2

Background
Syndecans are heparan sulfate proteoglycans that occur in membrane-bound or soluble forms. Syndecan-3, the least well-characterised of the syndecan family, is highly expressed on synovial endothelial cells in rheumatoid arthritis patients... Read More about Soluble syndecan-3 binds chemokines, reduces leukocyte migration in vitro and ameliorates disease severity in models of rheumatoid arthritis.

The in vitro effect of syndecan-3 gene knockout on bone marrow-derived mesenchymal stem cells' properties (2019)
Journal Article
Stefan, A., Kay, A. . G., Forsyth, N., Jones, F. . K., Pisconti, A., & Kehoe, O. (2019). The in vitro effect of syndecan-3 gene knockout on bone marrow-derived mesenchymal stem cells' properties. International Journal of Experimental Pathology, 99(6),

Introduction: Inflammation is a central feature of rheumatoid arthritis that affects around 1% of the population and can result in disability and morbidity. The immunomodulatory effects of bone marrow-derived mesenchymal stem cells (MSCs) have been w... Read More about The in vitro effect of syndecan-3 gene knockout on bone marrow-derived mesenchymal stem cells' properties.

Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis (2018)
Journal Article
Eustace, A., King, S., Sessions, R., Kay, A., Farris, M., Broadbridge, R., …McNaughton, E. (2018). Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis. The Journal of Immunology, 3201-3217. https://doi.org/10.4049/jimmunol.1701187

Inflammation is characterized by the infiltration of leukocytes from the circulation and into the inflamed area. Leukocytes are guided throughout this process by chemokines. These are basic proteins that interact with leukocytes to initiate their act... Read More about Novel Anti-Inflammatory Peptides Based on Chemokine-Glycosaminoglycan Interactions Reduce Leukocyte Migration and Disease Severity in a Model of Rheumatoid Arthritis.

Therapeutic Benefit for Late, but Not Early, Passage Mesenchymal Stem Cells on Pain Behaviour in an Animal Model of Osteoarthritis. (2017)
Journal Article
Chapman, V., Markides, H., Sagar, D., Xu, L., Kay, A., Burston, J., …El Haj, A. (2017). Therapeutic Benefit for Late, but Not Early, Passage Mesenchymal Stem Cells on Pain Behaviour in an Animal Model of Osteoarthritis. Stem Cells International, 2905104 - ?. https://doi.org/10.1155/2017/2905104

Background: Mesenchymal stem cells (MSCs) have a therapeutic potential for the treatment of osteoarthritic (OA) joint pathology and pain. The aims of this study were to determine the influence of a passage number on the effects of MSCs on pain behavi... Read More about Therapeutic Benefit for Late, but Not Early, Passage Mesenchymal Stem Cells on Pain Behaviour in an Animal Model of Osteoarthritis..