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Jay's research interests are on the extracellular matrices of articular cartilage and tendons.  His grant funded research in tendinopathies has been closely linked with the equine clinic and clinicians to enable the translation of the basic research to the clinic.  This has involved investigating age- and exercise-induced mechanisms of tendinopathies in the horse and has established ex vivo models of tendon injuries.  Recent work using such models has given insight into the mechanisms of failed healing seen in clinic for tendon injuries that are located within the tendon synovial sheath (intrasynovial injuries).  Current work is centred on the senescence associated secretory phenotype in equine tendon cells as a potential mechanism of age- and exercise-related tenon injuries.  His work in regenerative medicine has been to develop the therapeutic potential of mesenchymal stem cells for the repair of tendon injuries in large animal models of spontaneous and experimental tendon injuries.  Alongside this, he has been developing serological markers of the disease with equine clinical colleagues.

He has developed research with companion animal clinicians to investigate cardiac derived stem cells and induced pluripotent stem cells (iPSCs) with aim of translating their potential for heart repair or as in vitro (“disease in a dish”) models for developing and testing drugs.

His current research on cartilage is developing spectroscopic approaches for minimally invasive method of assessing early cartilage degeneration that is seen with osteoarthritis.  This patented approach to assess molecular alterations of the cartilage in very early disease prior to signs of erosion has led to Jay leading a proof-of-concept test of the successfully first-in-man use of the technology via minimally invasive surgery in the knees of osteoarthritis patients. Together with collaborators at University College London this technology is being taken forward for further technological and commercial development.

 

 

Selected publications & presentations

Smith EJ, Beaumont RE, Dudhia J, Guest DJ. Equine Embryonic Stem Cell-Derived Tenocytes are Insensitive to a Combination of Inflammatory Cytokines and Have Distinct Molecular Responses Compared to Primary Tenocytes. Stem Cell Rev Rep. 2024 May;20(4):1040-1059. doi: 10.1007/s12015-024-10693-8. Epub 2024 Feb 24. PMID: 38396222; PMCID: PMC11087315.

Tamura N, Heidari N, Faragher RGA, Smith RKW, Dudhia J. Effects of resveratrol and its analogues on the cell cycle of equine mesenchymal stem/stromal cells. J Equine Sci. 2023 Sep;34(3):67-72. doi: 10.1294/jes.34.67. Epub 2023 Sep 8. PMID: 37781569; PMCID: PMC10534064.

Esposito M, Astolfo A, Cipiccia S, Jones CM, Savvidis S, Ferrara JD, Endrizzi M, Dudhia J, Olivo A. Technical note: Cartilage imaging with sub-cellular resolution using a laboratory-based phase-contrast x-ray microscope. Med Phys. 2023 Oct;50(10):6130-6136. doi: 10.1002/mp.16599. Epub 2023 Jul 11. PMID: 37431640; PMCID: PMC10947188.

Melzer M, Burk J, Guest DJ, Dudhia J. Influence of Rho/ROCK inhibitor Y-27632 on proliferation of equine mesenchymal stromal cells. Front Vet Sci. 2023 Jun 6;10:1154987. doi: 10.3389/fvets.2023.1154987. PMID: 37346276; PMCID: PMC10279950.

Bizley, SC,  Dudhia, J,  Smith, RKW,  Williams, AC.  Transdermal drug delivery in horses: An in vitro comparison of skin structure and permeation of two model drugs at various anatomical sites. Vet Dermatol.  2023; 34: 235– 245. 

Marr N, Zamboulis DE, Werling D, Felder AA, Dudhia J, Pitsillides AA, Thorpe CT.  The tendon interfascicular basement membrane provides a vascular niche for CD146+ cell subpopulations. Front Cell Dev Biol. 2023 Jan 9;10:1094124. doi: 10.3389/fcell.2022.1094124. eCollection 2022.PMID: 36699014

Smith EJ, Beaumont RE, McClellan A, Sze C, Palomino Lago E, Hazelgrove L, Dudhia J, Smith RKW, Guest DJ. Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell-derived factors. Cell Tissue Res. 2023 Mar;391(3):523-544. doi: 10.1007/s00441-022-03726-6. Epub 2022 Dec 22.PMID: 36543895

Guest DJ, Dudhia J, Smith RKW, Roberts SJ, Conzemius M, Innes JF, Fortier LA, Meeson RL. Position Statement: Minimal Criteria for Reporting Veterinary and Animal Medicine Research for Mesenchymal Stromal/Stem Cells in Orthopedic Applications. Front Vet Sci. 2022 Mar 7;9:817041. doi: 10.3389/fvets.2022.817041. PMID: 35321059; PMCID: PMC8936138.

Marr N, Meeson R, Kelly E, Fang Y, Peffers MJ, Pitsillides AA, Dudhia J, Thorpe CT. CD146 delineates an interfascicular cell sub-population in tendon that is recruited during injury through its ligand laminin-α4. Int J Mol Sci. 2021 Sep 8;22(18):9729. doi: 10.3390/ijms22189729.

Intra-operative Raman spectroscopy and ex vivo Raman mapping for assessment of cartilage degradation. Gaifulina R, Nunn ADG, Draper ERC, Strachan RK, Firth S, Blake N, Thomas G, McMillan PF, Dudhia J. Clinical Spectroscopy 3 (2021) 100012. 

Ribitsch IM, Baptista PM, Lange-Consiglio A, Melotti L, Patruno M, Jenner F, Schnabl-Feichter E, Dutton L, Connolly DJ, Van, Steenbeek F, Dudhia J and Penning LC. Large animal models in regenerative medicine and tissue engineering: To do or not to do. Front. Bioeng. Biotechnol. Aug 13;8:972. doi: 10.3389/fbioe.2020.00972

Rashid M, Dudhia J, Dakin SG, Snelling S, Lach A, De Godoy R, Mouthuy PA, Smith R, Morrey M, Carr AJ. Histological evaluation of cellular response to a multifilament electrospun suture for tendon repair.  PLoS One. 2020 Jun 26;15(6):e0234982. doi: 10.1371/journal.pone.

Choi H, Simpson D, Wang D, Prescott M, Pitsillides AA, Dudhia J, Clegg PD, Ping P, Thorpe CT.  Heterogeneity of proteome dynamics between connective tissue phases of adult tendon.  eLife 2020;9:e55262. DOI: https://doi.org/10.7554/eLife.55262

Kelly E, Smith R, Dudhia J, Faragher RGA. Science-in-brief: The importance of senescence in tendinopathy: New opportunities.  Equine Vet J. 2020 May;52(3):349-351. doi: 10.1111/evj.13228.

Smith R, Önnerfjord P, Holmgren K, di Grado S, Dudhia J.  Development of a Cartilage Oligomeric Matrix Protein Neo-Epitope Assay for the Detection of Intra-Thecal Tendon Disease.  Int J Mol Sci. 2020 Mar 20;21(6). pii: E2155. doi: 10.3390/ijms21062155.

Rashid M, Dudhia J, Dakin SG, Snelling SJB, De Godoy R, Mouthuy PA, Smith RKW, Morrey M, Carr AJ. Histopathological and immunohistochemical evaluation of cellular response to a woven and electrospun polydioxanone (PDO) and polycaprolactone (PCL) patch for tendon repair. Sci Rep. 2020 Mar 16;10(1):4754. doi: 10.1038/s41598-020-61725-5.

Dutton LC, Dudhia J, Guest DJ, Connolly DJ. Inducing Pluripotency in the Domestic Cat (Felis catus).  Stem Cells Dev.  2019 Oct 1;28(19):1299-1309. doi: 10.1089/scd.2019.0142.

Khan MR, Smith RKW, David FH, Lam R, Hughes G, De Godoy R, Carr AJ, Goodship AE, Dudhia J.  Evaluation of synovium multipotent cells on deep digital flexor tendon repair in a large animal model of intra-synovial tendinopathy J Orthop Res. 2019 Jul 22. doi: 10.1002/jor.24423.

Dutton LC DJ, Catchpole B, Hodgkiss-Geere H, Werling D, Connolly DJ: Cardiosphere-derived cells suppress allogeneic lymphocytes by production of PGE2 acting via the EP4 receptor. Sci Rep, 2018 Sep 6;8(1):13351. doi: 10.1038/s41598-018-31569-1.

Khan MR, Dudhia J, David FH, De Godoy R, Mehra V, Hughes G, Dakin SG, Carr AJ, Goodship AE, Smith RKW.  Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium. Stem Cell Res Ther. 2018 Jun 19;9(1):169. doi: 10.1186/s13287-018-0900-7.

Dutton LC, Church SAV, Hodgkiss-Geere H, Catchpole B, Huggins A, Dudhia J, Connolly DJ: Cryopreservation of canine cardiosphere-derived cells: Implications for clinical application. Cytometry A 2018, 93(1):115-124.

Burk J, Brehm W, Smith RK, Dudhia J: Editorial to the Special Issue "Stem Cell Characterization Across Species". Cytometry A 2018, 93(1):16-18.

Yamamoto K, Santamaria S, Botkjaer KA, Dudhia J, Troeberg L, Itoh Y, Murphy G, Nagase H: Inhibition of Shedding of Low-Density Lipoprotein Receptor-Related Protein 1 Reverses Cartilage Matrix Degradation in Osteoarthritis. Arthritis Rheumatol 2017, 69(6):1246-1256.

Garvican ER, Salavati M, Smith RKW, Dudhia J: Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries. Connect Tissue Res 2017, 58(5):438-446.

Fields M, Spencer N, Dudhia J, McMillan PF: Structural changes in cartilage and collagen studied by high temperature Raman spectroscopy. Biopolymers 2017, 107(6).

Edmonds RE, Garvican ER, Smith RK, Dudhia J: Influence of commonly used pharmaceutical agents on equine bone marrow-derived mesenchymal stem cell viability. Equine Vet J 2017, 49(3):352-357.

Zaman G, Staines KA, Farquharson C, Newton PT, Dudhia J, Chenu C, Pitsillides AA, Dhoot GK: Expression of Sulf1 and Sulf2 in cartilage, bone and endochondral fracture healing. Histochem Cell Biol 2016, 145(1):67-79.

Yamamoto K, Okano H, Miyagawa W, Visse R, Shitomi Y, Santamaria S, Dudhia J, Troeberg L, Strickland DK, Hirohata Set al: MMP-13 is constitutively produced in human chondrocytes and co-endocytosed with ADAMTS-5 and TIMP-3 by the endocytic receptor LRP1. Matrix Biol 2016, 56:57-73.

Santamaria S, Fedorov O, McCafferty J, Murphy G, Dudhia J, Nagase H, Yamamoto K: Development of a monoclonal anti-ADAMTS-5 antibody that specifically blocks the interaction with LRP1. MAbs 2017, 9(4):595-602.

Khan MR, Chandrashekran A, Smith RK, Dudhia J: Immunophenotypic characterization of ovine mesenchymal stem cells. Cytometry A2016, 89(5):443-450.

Garvican ER, Cree S, Bull L, Smith RK, Dudhia J: Erratum to: Viability of equine mesenchymal stem cells during transport and implantation. Stem Cell Res Ther 2016, 7(1):161.

Clements LE, Garvican ER, Dudhia J, Smith RK: Modulation of mesenchymal stem cell genotype and phenotype by extracellular matrix proteins. Connect Tissue Res 2016, 57(6):443-453.

Dudhia J, Becerra P, Valdes MA, Neves F, Hartman NG, Smith RK: In Vivo Imaging and Tracking of Technetium-99m Labeled Bone Marrow Mesenchymal Stem Cells in Equine Tendinopathy. J Vis Exp 2015(106):e52748.

Borgeat K, Dudhia J, Luis Fuentes V, Connolly DJ: Circulating concentrations of a marker of type I collagen metabolism are associated with hypertrophic cardiomyopathy mutation status in ragdoll cats. J Small Anim Pract 2015, 56(6):360-365.

Bolton SN, Whitehead MP, Dudhia J, Baldwin TC, Sutton R: Investigating the Postmortem Molecular Biology of Cartilage and its Potential Forensic Applications. J Forensic Sci 2015, 60(4):1061-1067.

Yamamoto K, Owen K, Parker AE, Scilabra SD, Dudhia J, Strickland DK, Troeberg L, Nagase H: Low density lipoprotein receptor-related protein 1 (LRP1)-mediated endocytic clearance of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4): functional differences of non-catalytic domains of ADAMTS-4 and ADAMTS-5 in LRP1 binding. J Biol Chem 2014, 289(10):6462-6474.

Muller C, Khabut A, Dudhia J, Reinholt FP, Aspberg A, Heinegard D, Onnerfjord P: Quantitative proteomics at different depths in human articular cartilage reveals unique patterns of protein distribution. Matrix Biol 2014, 40:34-45.

Garvican ER, Dudhia J, Alves AL, Clements LE, Plessis FD, Smith RK: Mesenchymal stem cells modulate release of matrix proteins from tendon surfaces in vitro: a potential beneficial therapeutic effect. Regen Med 2014, 9(3):295-308.

Garvican ER, Cree S, Bull L, Smith RK, Dudhia J: Viability of equine mesenchymal stem cells during transport and implantation. Stem Cell Res Ther 2014, 5(4):94.

Dakin SG, Smith RK, Heinegard D, Onnerfjord P, Khabut A, Dudhia J: Proteomic analysis of tendon extracellular matrix reveals disease stage-specific fragmentation and differential cleavage of COMP (cartilage oligomeric matrix protein). J Biol Chem 2014, 289(8):4919-4927.

Dakin SG, Dudhia J, Smith RK: Resolving an inflammatory concept: the importance of inflammation and resolution in tendinopathy. Vet Immunol Immunopathol 2014, 158(3-4):121-127.

Chandrashekran A, Isa I, Dudhia J, Thrasher AJ, Dibb N, Casimir C, Readhead C, Winston R: Lentiviral vector transduction of spermatozoa as a tool for the study of early development. FEBS Open Bio 2014, 4:266-275.

Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J: Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy. PLoS One 2013, 8(9):e75697.

Manning HB, Nickdel MB, Yamamoto K, Lagarto JL, Kelly DJ, Talbot CB, Kennedy G, Dudhia J, Lever J, Dunsby Cet al: Detection of cartilage matrix degradation by autofluorescence lifetime. Matrix Biol 2013, 32(1):32-38.

Dakin SG, Dudhia J, Smith RK: Science in brief: resolving tendon inflammation. A new perspective. Equine Vet J 2013, 45(4):398-400.

Becerra P, Valdes Vazquez MA, Dudhia J, Fiske-Jackson AR, Neves F, Hartman NG, Smith RK: Distribution of injected technetium(99m)-labeled mesenchymal stem cells in horses with naturally occurring tendinopathy. J Orthop Res 2013, 31(7):1096-1102.

Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK: Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet J 2012, 44(1):25-32.

Dakin SG, Werling D, Hibbert A, Abayasekara DR, Young NJ, Smith RK, Dudhia J: Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair. PLoS One 2012, 7(2):e32333.

Dakin SG, Dudhia J, Werling NJ, Werling D, Abayasekara DR, Smith RK: Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease. PLoS One 2012, 7(11):e48978.

Smith MR, Wright IM, Minshall GJ, Dudhia J, Verheyen K, Heinegard D, Smith RK: Increased cartilage oligomeric matrix protein concentrations in equine digital flexor tendon sheath synovial fluid predicts intrathecal tendon damage. Vet Surg 2011, 40(1):54-58.

Dart AJ, Dart CM, Dudhia J, Perkins N, Canfield P, Smith RK: A preliminary study on the effect of wounding on transforming growth factor-beta1 and cartilage oligomeric matrix protein concentrations in the skin of horses. Vet Surg 2011, 40(1):59-65.

Dakin SG, Jespers K, Warner S, O'Hara LK, Dudhia J, Goodship AE, Wilson AM, Smith RK: The relationship between in vivo limb and in vitro tendon mechanics after injury: a potential novel clinical tool for monitoring tendon repair. Equine Vet J 2011, 43(4):418-423.

Alves AG, Stewart AA, Dudhia J, Kasashima Y, Goodship AE, Smith RK: Cell-based therapies for tendon and ligament injuries. Vet Clin North Am Equine Pract 2011, 27(2):315-333.

Recent book chapters

“Tendons and Ligaments” JAYESH DUDHIA, CHAVAUNNE T. THORPE, NEIL MARR, ROGER K.W. SMITH, published in "Essential Facts of Equine Physical Therapy, Rehabilitation and Sports Medicine". João Paulo Marques (Editor) • Steve Adair, Hilary Clayton • Kevin Haussler • Johann Maierl, 2024, ISBN 978-3-938274-31-6

Selected presentations

·     Plenary lecture at the The Third Achilles Workshop, Porto, Portugal, 25 – 27 October 2021.  “Cell stressors in tendinopathies and implications for repair strategies.”

·     International Panel Member on the VAIBHAV Global Summit, India, for “New generation Veterinary International Panel Member on the VAIBHAV Global Summit, India, for “New generation Veterinary therapeutics" within the “Agro Economy and Food Security” theme, and presentation “Challenges in Veterinary Regenerative Medicine”, 20th October 2020; virtual conference. 

·     “The application of stem cells in veterinary medicine” Invited webinar, University of Malaysia Kelantan, Faculty of Veterinary Medicine, 22nd June 2020;

·     “Extracellular vesicles of MSCs and topographical cues for the modulation of tendon inflammation” Invited talk, European Orthopaedic Research Society, 27th Annual Meeting, Maastricht 2nd – 5th October 2019;

·     “Cardiosphere-derived cells for allogeneic stem cell therapy in canine dilated cardiomyopathy”. Keynote, TERMIS EU 2019, 27th - 31st May 2019, Rhodes, Greece;

·     “Stem cells, conservation, collaboration”. Talk to senior management of Mawarid Services, which is a part of Mawarid Holdings, an investment company with diverse interests.  A major focus of Mawarid Services is conservation of endangered species.  24th March 2019, Al Ain, UAE;

·     “Cell based therapies at the ÌÇÐÄvlogÊÓƵ” Talk to the United Arab Emirates University, at the College of Food and Agriculture and to the Veterinary Department (talk to the Dean, HoD and academic staff to promote collaborations in the Regenerative Medicine field), 17th February 2019, Al Ain, UAE;

·     “Label free imaging of articular cartilage”.  Invited talk at the Equine Veterinary Medical Centre, 17th October 2018, Doha, Qatar;

·     "Mesenchymal stem cell derived extracellular vesicles to modulate the tendon microenvironment in repair strategies" Keynote, European Orthopeadic Society 26th Annual meeting, 26th October 2018 Galway, Ireland;

·     “Large animal translational models for orthopaedics", Seminar at the 3B's (Biomaterials, Biodegradables and Biomimetics) Research Group, Department of Polymer Engineering, University of Minho, 23rd February 2018;

·     "Upsizing the lab: experiences with large animal translational models of tendinopathies". 2 – 7th July 2018, Keynote, TERMIS Annual Meeting, Kyoto, Japan;

·     “Role of hyperthermia in the development of tendinopaties” Invited talk, 15 – 19th October 2018, Third Havemeyer Symposium on Tendons, Colorado, USA;

·     “Investigating the tendon microenvironment to develop engineered bioscaffolds for cell-based therapies” European Orthopeadic Research Society 25th Annual meeting, 13th October 2017, Munich, Germany;

·     “Tendon Therapy – How relevant are small and large animal models” Keynote, 28th Annual Conference of the European Society for Biomaterials, 13 September 2017, Athens, Greece;

 

 

Jay holds a Postgraduate Certificate in Veterinary Education and is a Member of the Higher Education Academy.  He teaches on the BSc BioVeterinary Sciences, BVetMed and Gateway to BVetMed programmes on extracellular matrix biology, development, structure and function of cartilage and tendons and associated pathologies in man and equids. He also supervises laboratory based projects for BSc (years 2 and 3) and BVetMed undergraduates (RP2 rotation).  Jay acts as a departmental or non-departmental assessor for the annual appraisal system at the RVC for PhD students.

He has previously taught at UCL, Institute of Orthopaedics on the Intercalated BSc, MSc and distance learning programmes.

Jay is particularly interested in clinical applications of his research and has successful collaborations with both veterinary clinicians within the RVC animal hospitals as well as medical colleagues outside.  He has developed a programme of research with small animal clinicians on applications of stem cells in feline and canine myocardial diseases, and the stem cell laboratory that he established was with the aim of providing a clinical service in conjunction with the RVC animal hospitals and private veterinary clinics.

• CornealCellVision: Derivation of corneal keratocytes from canine induced pluripotent stem cells to develop disease models and novel treatments for corneal disease

  

  This project will generate corneal stromal tissue in the laboratory to pave the way to the development of an artificial cornea for future disease modelling and clinical transplantation into injured and diseased dog eyes to restore vision. . Corneal diseases are one of the most common debilitating source of visual loss that may lead to permanent blindness in humans as well as in animals. 

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• Understanding the genetic basis of catastrophic bone fracture in Thoroughbred horses using stem cells.

  

  Bone fractures are a significant welfare problem in the Thoroughbred racing industry. Previous work has demonstrated that fracture is a complex condition with both environmental and genetic factors risk factors. However, the specific genetic factors that underpin fracture risk have not been identified. This has proved problematic to work out using patients due to the difficulty in accessing bone tissue and the large variability in exposure to environmental risk factors.

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• Using pluripotent stem cells to improve tendon regeneration in horses

  

  Tendon injuries are common in horses taking part in a wide range of disciplines. After an injury, adult tendons undergo poor natural regeneration, instead repairing with functionally inferior scar tissue which leads to high re-injury rates. 

  Improving tendon regeneration is therefore key to reducing re-injury rates and enabling more horses to return to work following an injury.

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