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Cartilage derived from equine induced pluripotent stem cells: an in vitro and ex vivo One Medicine approach for osteoarthritis

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A new approach to treating equine joint pain

Research on the use of induced pluripotent stem cells for treating arthritis in horses could also benefit human health.

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Joint pain is by no means limited to humans – horses experience arthritis too. “As a sporting and companion animal that provides immense economic and societal value, we have a duty to care for the well-being of horses,” says Laura Barrachina Porcar, a researcher at the University of Galway and Marie Skłodowska-Curie fellow. Helping treat equine arthritis are initiatives such as the EU-funded CAREQiPSC project. “Because of the many similarities between equine and human joints, advances made in veterinary care have the potential to benefit both species,” adds Frank Barry, a professor of cellular therapy at the University of Galway, who coordinated the project.

Introducing induced pluripotent stem cells

To advance how we treat arthritis in horses, the project proposed an innovative strategy for generating a novel and important type of stem cell called induced pluripotent stem cells (iPSCs). According to Barry, what makes iPSCs unique is their ability to differentiate into the specialised cells of the articular cartilage. “iPSCs have received a great deal of attention because they have the characteristics of embryonic stem cells but are not derived from embryonic tissues,” he explains. Instead, iPSCs are produced by programming tissue cells (e.g. from skin or blood) back to a state similar to that in the embryo. “This state is known as pluripotent, meaning that the cells have the potential to differentiate into multiple types of specialised cells,” adds Porcar.

Proving the potential of iPSCs for cell therapy of the joint

As is often the case in research, generating iPSCs in horses proved more challenging than expected. “We often try to extrapolate knowledge of cell biology from one species to another, but the particular biological attributes of different species should not be overlooked,” notes Porcar. Both for the generation of iPSCs and for their differentiation into cartilage cells, the researchers needed to adapt multiple protocols until they found the right conditions for equine cells. Once that was done, they were able to demonstrate, for the first time in a horse, that the generation of iPSCs is highly dependent on the initial type of tissue cell being used. “We observed that the less mature the cell, the more easily it goes back to a pluripotent state,” remarks Barry. Also for the first time in horses, researchers were able to differentiate iPSCs into cartilage cells by following various differentiation pathways.

Benefiting horses and possibly people too

Although the protocols for differentiation still need fine-tuning, Porcar says the project has proven the potential of iPSCs for cell therapy of the joint. “Observing the successful formation of these cells was probably the proudest moment of the project, especially considering the still limited knowledge on these cells in horses,” she explains. Having established several lines of equine iPSCs, the research team is now looking at their differentiation into other types of specialised cells that can be used to study pathologies or to treat different conditions. “The CAREQiPSC project established the basis for a more robust generation of iPSCs in horse and has opened the door for their application to study and treat joint pathologies,” concludes Barry. “This knowledge can now be used to exploit the extraordinary potential of these special stem cells for many exciting applications not only in animals, but possibly people too.”

Keywords

CAREQiPSC, induced pluripotent stem cells, equine joint pain, stem cells, arthritis, horses, health, veterinary care, cell therapy

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