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Dr Debbie Guest

Abstract:

We have two main areas of research. Firstly, the development of new treatments to aid tendon regeneration in horses. Horses suffer from a high number of tendon injuries. They heal through the formation of scar tissue which leads to a high rate of re-injury. Clinically autologous mesenchymal stem cells (MSCs) are being used to aid tendon regeneration but little is known about their mechanism of action. Our previous work demonstrated a poor long-term tissue integration of MSCs suggesting that they do not make a direct, physical contribution to tissue repair through differentiation. Instead, evidence suggests that MSCs may function through modulation of injury-induced inflammation.  In contrast, pluripotent equine embryo-derived stem cells (ESCs) have a high survival in the injured tendon and appear to undergo differentiation to tenocytes. We are now working to understand the pathways underpinning the different mechanism of stem cell function in tendon repair.     Secondly, we have derived induced pluripotent stem cells (iPSCs) from horses and dogs to allow the in vitro modelling of inherited diseases. For example, fractures occur frequently in racing Thoroughbred horses. Although we have demonstrated that fracture risk has a genetic component, it is a complex disorder with multiple genes involved. We hypothesise that a high risk genotype confers susceptibility to fracture through sub-optimal bone remodelling in response to exercise. We are currently using equine iPSCs to test this hypothesis in vitro by performing bone differentiation of iPSCs derived from horses at high and low risk of fracture.

References:

  1. 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.    
  2. 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.    
  3. 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.

Dr Debbie Guest

Dr Debbie Guest
Animal Health Trust
Office Phone: 01638 751000 ext 1283