Stem Cell Research
Stem cells have the ability to self-renew and to turn into other types of cells. We are carrying out research into their potential use in veterinary medicine.
We are currently researching stem cell therapy for horse tendon injuries and fractures in Thoroughbreds.
Read our latest publications on our stem cell research.
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Stem cells have the ability to self-renew to generate more stem cells and to turn into other types of cells. Broadly, stem cells can be classified into two groups; multipotent stem cells and pluripotent stem cells. Multipotent or “adult” stem cells exist in many different tissues and can only turn into a limited number of cell types. In contrast pluripotent or “embryonic” stem cells exist at the very earliest stages of development and can turn into every cell type of the body.
We are carrying out research to use stem cells in veterinary medicine. To date our research has focused on horses and dogs and we have derived pluripotent stem cells from horse embryos and multipotent stem cells from adult horse and dog tissues.
Horse embryo-derived stem cells (ES cells) can be grown indefinitely in the laboratory, express markers associated with pluripotency and can turn many different types of cells. This means they have the potential to be used therapeutically to help regenerate damaged tissues. We have also made horse and dog induced pluripotent stem cells (iPS cells) from adult cells by reprogramming them back to a state where they resemble ES cells. Like ES cells, iPS cells have the potential to be used therapeutically. Furthermore, iPS cells can be isolated from horses and dogs with inherited diseases in order to provide a tool to study that disease in the laboratory.
Horse multipotent mesenchymal stem cells (MS cells) can be isolated from many tissues including the bone marrow and fat tissue of adult horses and the umbilical cord blood of new-born foals.
Tendon injuries occur commonly in racing and sport horses and because the injuries heal through the formation of scar tissue instead of normal tendon tissue they are associated with a high rate of re-injury. Stem cells may help to bring about normal tendon regeneration and therefore reduce the frequency of re-injury. Our research aims to understand the mechanisms by which different types of stem cells work so that we can produce an optimised stem cell therapy for horse tendon injuries.
In current clinical practice horses are treated with their own mesenchymal stem (MS) cells. This requires each horse to have a tissue sample isolated and results in a delay while the cells are processed and grown to sufficient numbers for injection into the tendon. The advantage of embryo-derived stem (ES) cells is that they grow indefinitely in the laboratory and may therefore provide an “off the shelf” source of cells for treating injuries.
We have shown that ES cells can be injected into the damaged tendons of horses without any undesirable side effects being detected in the 3 month period studied. The ES cells survive in high and stable numbers in the tendon and turn into tendon cells. In the laboratory we have established a 3D culture system to generate artificial tendons from ES cells. We are using this system to determine the signals which drive ES cells to turn into tendon cells to ensure that therapies which use ES cells in the future will be safe and effective.
In contrast to ES cells, MS cells do not turn into tendon cells following their injection into the tendon. However, we have shown that horse MS cells are able to reduce an inflammatory response and they may produce other signals which act to stimulate better tissue regeneration by the body’s own cells.
Fractures in Thoroughbreds:
Fractures caused by bone overloading (as opposed to a direct trauma) are common in racing Thoroughbreds. The risk of fractures is affected by various environmental factors but previous work at the AHT has shown that there is also a genetic risk to fracture in Thoroughbreds.
We are now using iPS cells from horse at high and low genetic risk of fracture to generate bone in the laboratory. This will allow us to determine the biological mechanisms which are affected in high risk horses and understand why these horses are predisposed to fracture.
In the future this will enable the design and application of management techniques to minimise the risk of fracture in horses.
Making dog corneal cells in the laboratory
The cornea allows light to be transmitted into the eye. In corneal stromal dystrophy, fat deposits inside the tissue and can lead to ulceration and impaired sight. It occurs in many dog breeds and there are no treatment options available. Corneal transplantation is hampered by a shortage of donor material.
We are carrying out research to study corneal stromal stem cells and produce corneal stromal cells in the laboratory from dog induced pluripotent stem cells (iPSCs). These cells will provide a new tool to enable future studies of this disease to better understand what causes it and if it could be prevented.
The production of corneal cells may also provide a new transplantation therapy for dogs with corneal damage resulting from injury or disease. This work is being performed in collaboration with Professor Julie Daniels, Institute of Ophthalmology, University College London.
Bavin Emma P., Atkinson Francesca, Barsby Tom, and Guest Debbie J.. Stem Cells and Development. January (2017) Scleraxis Is Essential for Tendon Differentiation by Equine Embryonic Stem Cells and in Equine Fetal Tenocytes
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.
Broeckx, S.Y, Borena, B.,Van Hecke, L., Chiers, K., Maes, S., Guest, D.J., Meyer, E., Duchateau, L., Martens, A., & Spaas, J.H. (2015) Comparison of autologous versus allogeneic epithelial-like stem cell treatment in an in vivo equine skin wound model. Cytotherapy. 17(10):1434-46
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.
Broeckx, S., de Vries, C., Suls, M., Guest, D. J., Spaas, J. H. (2013) Guidelines to Optimize Survival and Migration Capacities of Equine Mesenchymal Stem Cells. J Stem Cell Res Ther 3: 147.
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.
Spaas, J. H., Guest, D. J., Van de Walle, G. R. (2012) Tendon Regeneration in Human and Equine Athletes: Ubi Sumus-Quo Vadimus (Where are We and Where are We Going to)? Sports Medicine. 42(10)871-890.
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.
Greenway, D. J. & Allen, W. R. (2007). Horse stem cells in development and therapies. Reproduction in Domestic Animals. 42(Suppl. 2) 68-68.
For further information please contact
Dr Debbie Guest
+44(0)1638 750000 ex. 1283
Write to us at:
Animal Health Trust