Debbie’s research is centred around the pluripotent stem cells from companion animals (horses, dogs and cats). She has derived and characterised horse embryonic stem cells and has an established research programme to develop novel cell therapies for tendon injuries in horses. Debbie’s group have established 3 dimensional culture protocols for the differentiation of embryonic stem cells into tendon cells and have performed detailed characterisation of the cells to determine their safety and efficacy in tendon regeneration. Her current focus is to identify the mechanisms by which embryonic stem cell derived tendon cells are protected from the effects of inflammation to develop novel drug treatments to aid adult tendon regeneration.

Debbie has also derived induced pluripotent stem cells from horses, dogs and cats to develop “disease in a dish models” to understand the genetic basis for inherited diseases with the aim of developing new interventions and treatments. Her primary focus is on catastrophic bone fractures in Thoroughbred horses, but she is also part of collaborative projects using iPSCs for heart disease in cats and corneal disease in dogs.

Ross E. Beaumont, Emily J. Smith, Clara David, Yasmin Z. Paterson, Elena Faull, Deborah J. Guest. Equine adult, fetal and ESC-tenocytes have differential migratory, proliferative and gene expression responses to factors upregulated in the injured tendon, Cells & Development (2025) 181, 204003. doi.org/10.1016/j.cdev.2025.204003.

Palomino Lago E, Ross AKC, McClellan A, Guest DJ. Identification of a global gene expression signature associated with the genetic risk of catastrophic fracture in iPSC-derived osteoblasts from Thoroughbred horses. Anim Genet. 2025 Feb;56(1):e13504. doi: 10.1111/age.13504. PMID: 39801206.

Guest DJ, Birch HL, Thorpe CT. A review of the equine suspensory ligament: Injury prone yet understudied. Equine Vet J. 2024 Nov 27. doi: 10.1111/evj.14447. Epub ahead of print. PMID: 39604165.

Dutton L.C., Dudhia J., Guest D.J. & Connolly D.J. (2024) CRISPR/Cas9 gene editing in induced pluripotent stem cells to investigate the feline hypertrophic cardiomyopathy causing MYBPC3/R820W mutation. PloS One 19, e0311761

Smith, E. J., Beaumont, R. E., Dudhia, J. & Guest, D. J. 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, May;20(4):1040-1059. doi:10.1007/s12015-024-10693-8 (2024).

E. Palomino Lago, A. Baird, S. C. Blott, R E McPhail, A. C. Ross, D. J Guest. A Functional Single-Nucleotide Polymorphism Upstream of the Collagen Type III Gene Is Associated with Catastrophic Fracture Risk in Thoroughbred Horses. Animals 2024, 14, 116. https://doi.org/10.3390/ani14010116

Palomino Lago, E., Jelbert, E. R., Baird, A., Lam, P. Y. & Guest, D. J. Equine induced pluripotent stem cells are responsive to inflammatory cytokines before and after differentiation into musculoskeletal cell types. In Vitro Cellular & Developmental Biology - Animal, doi:10.1007/s11626-023-00800-3 (2023).

Beaumont RE, Smith EJ, Zhou L, Marr N, Thorpe CT, Guest DJ. Exogenous interleukin-1 beta stimulation regulates equine tenocyte function and gene expression in three-dimensional culture which can be rescued by pharmacological inhibition of interleukin 1 receptor, but not nuclear factor kappa B, signaling. Molecular and Cellular Biochemistry. 2023. doi: 10.1007/s11010-023-04779-z

E. J. Smith, R. E. Beaumont, A. McClellan, C. Sze, E. Palomino Lago, L. Hazelgrove, J. Dudhia, R.K. Smith, D. J. Guest (2022) "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 and Tissue Research, doi: 10.1007/s00441-022-03726-6.

D. J. Guest, J. Dudhia, R. K. Smith, S. Roberts,  M. Conzemius, J.F. Innes, L. Fortier and R. L. Meeson. (2022) Position Statement: Minimal criteria for reporting veterinary and animal medicine research for mesenchymal stromal/stem cells in orthopaedic applications. Frontiers in Veterinary Science. 9, 10.3389/fvets.2022.817041.

Paterson, YZ, Evans N, Kan S, Cribbs A, Henson FMD, Guest DJ (2020). The transcription factor scleraxis differentially regulates gene expression in tenocytes isolated at different developmental stages. Mech Dev. 163, 103635.

Paterson, YZ, Cribbs A, Espenel M, Smith EJ, Henson FMD, Guest DJ (2020). Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes. Stem Cell Res Ther. 11 (1):184.

Atkinson F, Evans R, Guest JE, Bavin EP, Cacador D, Holland C, Guest DJ (2020). Cyclical strain improves artificial equine tendon constructs in vitro. J Tissue Eng Regen Med. 2020 14(5):690-700. 

Kafarnik, C., McClellan, A., Dziasko, M., Daniels, J. T., Guest, D. J. (2020). Canine Corneal Stromal Cells have multipotent mesenchymal stromal cell properties in vitro. Stem Cells Dev. 29(7):425-439.

McClellan, A., Paterson, Y. Z., Paillot, R. & Guest, D. (2019).Equine fetal, adult and embryonic stem cell derived tenocytes are all immune privileged but exhibit different immune suppressive properties in vitro. Stem Cells Dev. 28(21), 1413-1423. 

Dutton, L., Dudhia, J., Guest, D. J. and Connolly, D. J. (2019) Inducing pluripotency in the domestic cat (Felis Catus). Stem Cells Dev. 28(19),1299-1309.

McClellan, A., Evans, R., Sze, C., Kan, S., Paterson, Y., and Guest, D.J. (2019). A novel mechanism for the protection of embryonic stem cell derived tenocytes from inflammatory cytokine interleukin 1 beta. Scientific Reports 9(1), 2755.

Baird, A., Dominguez-Falcon, N., Saeed, A., and Guest, D. J. (2019). Biocompatible 3D printed thermoplastic scaffolds for osteoblast differentiation of equine iPS cells. Tissue Eng Part C Methods. 25(5), 253-261.

Baird, A., Lindsay, T., Everett, A., Iyemere, V., Paterson Y. Z., McClellan, A., Henson, F.M.D. & Guest, D. J. (2018) Osteoblast differentiation of equine induced pluripotent stem cells. Biology Open. doi: 10.1242/bio.033514. 10;7(5).

Paterson, Y. Z., Kafarnik, C. & Guest, D. J. (2018) Characterisation of companion animal pluripotent stem cells. Cytometry A. 93(1), 137-148.

Bavin, E. P., Atkinson, F., Barsby, T. & Guest, D. J. (2017) Scleraxis is essential for tendon differentiation by equine embryonic stem cells and in equine fetal tenocytes. Stem Cells and Development. 26(6):441-450.

Bavin, E. P, Smith, O., Baird, A.E, Smith, L.C., & Guest, D.J. (2015) Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells. Frontiers in Veterinary Science, 2, 55.

Baird, A.E.G, Barsby, T. & Guest, D.J. (2015) Derivation of canine induced pluripotent stem cells. Reproduction in Domestic Animals. ;50(4):669-76.

Paterson Y. Z., Rash, N., Garvican, E. R., Paillot, R., & Guest, D.J. (2014) Equine mesenchymal stromal cells and embryo-derived stem cells are immune privileged in vitro. Stem Cell Research and Therapy. 5, 90.

Barsby, T., Bavin, E. & Guest D. J. (2014) 3-Dimensional Culture and Transforming Growth Factor Beta3 Synergistically Promote Tenogenic Differentiation of Equine Embryo-Derived Stem Cells. Tissue Engineering Part A. 20, 2604-2613.

Barsby, T. & Guest, D. J. (2013) Transforming Growth Factor Beta3 Promotes Tendon Differentiation of Equine Embryo-Derived Stem Cells. Tissue Engineering Part A. 19(19-20)2156-2165.

Guest, D. J., Smith, M. R. W. & Allen, W. R. (2010) Equine embryonic stem-like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendons. Equine Veterinary Journal. 42(7), 636-642.

Guest, D. J., Ousey, J. C., and Smith, M. R. W. (2008) Defining the expression of marker genes in equine mesenchymal stromal cells.  Stem Cells and Cloning: Advances and Applications.  1, 1-9.

Guest, D. J., Smith, M. R. W., and Allen, W. R. (2008).  Monitoring the fate of autologous and allogeneic mesenchymal progenitor cells injected into the superficial digital flexor tendon of horses: preliminary study.  Equine Veterinary Journal.  40, 178-181.

Guest, D. J. and Allen, W. R. (2007).  Expression of cell-surface antigens and embryonic stem cell pluripotency genes in equine blastocysts.  Stem Cells and Development. 16, 789-795.

 

 

 

Debbie supervises both undergraduate and post-graduate research student projects.

Debbie has been a STEM (science, technology, engineering and maths) ambassador since 2011 to engage pupils in all stages of education with science.

• 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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