Using pluripotent stem cells to improve tendon regeneration in horses

Tendon injuries are common in horses. Tendons undergo poor natural regeneration, resulting in scar tissue which leads to high re-injury rates and the early retirement of many horses.

Horse ESCs growing in the laboratory

Challenge

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. The process of scar tissue formation is not fully understood, but significant levels of inflammation are produced in response to a tendon injury and this has negative effects on tendon cell function.

Tendon injuries are the number one reason for retirement from racing and they are the primary cause of veterinary-related career breaks in sport horses. Improving tendon regeneration is therefore key to reducing re-injury rates and enabling more horses to return to work following an injury.

Artificial tendons created from horse ESCs in the laboratory

Solution

Adult stem cells can be used to aid tendon repair in horses. However, rather than turn into tendon cells, they function by reducing inflammation in the tendon. In contrast, we have shown that horse embryonic stem cells (ESCs) can turn into tendon cells in the injured horse tendon. Furthermore, these cells appear to be protected from the effects of inflammation. This may be due to the embryonic origin of the cells, and research into other types of pluripotent stem cells (induced pluripotent stem cells) is ongoing.

Our research aims to develop new cell based therapies using pluripotent stem cells to enable improved tendon regeneration. We are also investigating novel methods to protect tendon cells from the adverse effects of inflammation.

Impact

Horse pluripotent stem cells express specific markers

The development of novel therapies for treating tendon injuries in horses would allow more horses to return to work following an injury and therefore have a significant welfare impact.

Furthermore, the horse provides a useful large animal model for human tendon injuries, offering the potential for our work to be translated to also improve human health.







Partners

We thank the Horserace Betting Levy Board (VET/RS/257) and the Petplan Charitable Trust (S19-747-786, S21-1022-1061, S20-921-960 and S21-962-1001) for funding this work.

Publications

Title Publication Year
The transcription factor scleraxis differentially regulates gene expression in tenocytes isolated at different developmental stages Mechanisms of Development 2020
Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes Stem Cell Res Ther 2020
Cyclical strain improves artificial equine tendon constructs in vitro J Tissue Eng Regen Med. 2020
Synthesis and formulation of four-arm PolyDMAEA/siRNA polyplex for transient downregulation of collagen type III gene expression in TGF-β1 stimulated tenocyte culture ACS Omega 2020
Equine fetal, adult and embryonic stem cell derived tenocytes are all immune privileged but exhibit different immune suppressive properties in vitro Stem Cells Dev 2019
A novel mechanism for the protection of embryonic stem cell derived tenocytes from inflammatory cytokine interleukin 1 beta Scientific Reports 2019
Characterisation of companion animal pluripotent stem cells Cytometry A 2018
Equine mesenchymal stromal cells and embryo-derived stem cells are immune privilegedin vitro Stem Cell Research and Therapy 2014
3-Dimensional Culture and Transforming Growth Factor Beta3 Synergistically Promote Tenogenic Differentiation of Equine Embryo-Derived Stem Cells Tissue Engineering Part A 2014
Guidelines to Optimize Survival and Migration Capacities of Equine Mesenchymal Stem Cells J Stem Cell Res Ther 3 2013
Transforming Growth Factor Beta3 Promotes Tendon Differentiation of Equine Embryo-Derived Stem Cells Tissue Engineering Part A 2013
Tendon Regeneration in Human and Equine Athletes: Ubi Sumus-Quo Vadimus (Where are We and Where are We Going to)? Sports Medicine 2012
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 2010
Defining the expression of marker genes in equine mesenchymal stromal cells Stem Cells and Cloning: Advances and Applications 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 2008
Expression of cell-surface antigens and embryonic stem cell pluripotency genes in equine blastocysts Stem Cells and Development 2007
Horse stem cells in development and therapies Reproduction in Domestic Animals 2007

Top of page