Named for their ability to branch out to become cells that build multiple kinds of tissue, mesenchymal stem cells (MSC) and mesenchymal stromal cells appear in embryos and adult bone marrow, respectively. In 2019 scientists suggested redefining the MSC acronym as medicinal signaling cells, because the therapeutic cells usually come from bone marrow rather than the mesenchymea part of embryos. In this article well refer to all these similar cell types as stem cells.

Twenty years ago biologists had successfully developed stem cells into cartilage, tendon, heart, bone, and other kinds of tissues in their laboratoriesspurring hope for unprecedented tissue repair therapies in humans and animals.

Scientists now know stem cells use a very different healing mechanism than previously suspected, Oosterlinck says. In fact, recent research has revealed its not what these cells become that matters, but what they doand, more specifically, how they do it, in large part through a process known as paracrine signaling.

Basically, theres a lot of crosstalk that happens between stem cells and the injured cells, Schnabel says. That crosstalk seems to recruit special cells within the injured tissue called progenitor cellsand those appear to develop into the original local tissue cells, such as tendon cells.

Some research groups are looking at ways to predifferentiate cells in a laboratorypreparing them to go into tendon versus cartilage tissue, for exampleto help encourage them to be more effective in their therapeutic environment, Oosterlinck says.

Meanwhile, other research teams are showing how stem cells trigger specific cytokines (cell-signaling proteins) and growth factors that contribute to better tissue healing, he says.

The cells also encourage vascularization, says Schnabel. They actually bring blood vessels into the area, promoting angiogenesis, she says.

These recent discoveries about stem cell functions are major breakthroughs, says Schnabel. Her team currently focuses on optimizing the use of these cells. One thing theyre homing in on is dosing, which has always been complex, especially in horses, because its impossible, she says, to achieve the per-pound dose of cells recommended in human medicine.

Theyre also fine-tuning the question of treatment timing, she says. Traditionally, clinicians have treated horses with stem cells once the initial inflammatory response from the injury subsides. The idea was that you dont want to cause more inflammation, potentially, and have an even lamer horse, and you dont want the stem cells to get killed by the inflammation, she explains.

Ultimately, that might not be the right approach. All the studies weve been doing actually suggest the opposite, that having them in an inflammatory environment is good, because it further primes the cells to secrete the things you want, she says.

Then that also begs the question, if you get a horse after the time of acute inflammation, could you prime the cells first in the lab so that theyre ready to go when you put them in the horse? she adds. And thats been a major focus of our work. We have a lot of strong preliminary data suggesting that thats true.

Schnabels team, as well as other research groups, have looked specifically at tendon healing, revealing that horses treated with stem cells have significantly reduced re-injury rates, especially in the superficial digital flexor tendon (SDFT)which has a traditional re-injury rate of up to 70% in racehorses (RK Smith, et al.). This is huge, she says.

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What's New in Equine Orthobiologics? The Horse - TheHorse.com