With any new veterinary treatment approach there come research studies, experiences, and opinions about what works best and why. Stem cell therapy is no exception. One veterinarian recently reported that at least for tendon injuries, the cases practitioners choose to target with stem cells and how they prepare those cells have more bearing on treatment success than the stem cell source they select.
Roger KW Smith, VetMB, PhD, DEO, FHEA, DECVS, MRCVS, professor of Equine Orthopaedics at the Royal Veterinary College, in Hatfield, U.K., shared this and more about what he and his colleagues have learned about stem cell treatment at the 2014 American Association of Equine Practitioners Convention, held Dec. 6-10 in Salt Lake City, Utah.
Mesenchymal stem cells (MSCs) can come from a variety of sources, though practitioners most often use bone marrow or fat (also termed adipose-derived stem cells). Umbilical cord cells and fetal tendon cells have come on the scene more recently, he added.
Cells can come from the horse that’s being treated (autologous therapy) or from a bank (allogeneic), though veterinarians in the U.K. are restricted to autologous because the U.K. does not currently allow allogeneic stem use, as the United States does.
But he does choose his cases. “The only requirement, really, for this particular treatment is a contained defect in a tendon or ligament,” he said. In other words, he and colleagues ideally want to treat a structure with a “central cavity surrounded by intact tendon tissue that can act as a receptacle” for the stem cells. The superficial digital flexor tendon (SDFT) is ideal because injuries to this structure generally meet this description and “because it’s the most common and for which we had comparative outcome for other treatments.” There is no minimal requirement for lesion size but veterinarians don’t generally inject smaller lesions because they have a better prognosis and are more difficult to inject. Stem cells are often focused on the most severe injuries.
Smith avoids treating traumatic injuries--those associated with external trauma to the leg, such as a cut or blunt trauma, rather than an overstrain injury due to overloading of the limb with prior tendon degeneration--with stem cells because studies have shown that open defects in tendons do not retain any implanted stem cells. However, if he feels there is enough time for a granulation tissue bed to form in the defect, then treatment is possible and can be effective. Timing is important; generally, the earlier he treats the injury with stem cells, the better the outcome.
Access to allogeneic stem cells would mean that, yes, he could implant them earlier. But the lag time before first treatment with autologous cases (about three weeks, due to the time it takes to aspirate bone marrow and expand the cells in the lab) isn’t all bad news because it gives the body a chance to establish a vascular supply to support cells after implantation. This usually happens within one or two weeks after injury.
As for selecting MSC cell type, again, he focuses on preparation rather than source. Smith classifies MSCs as either minimally manipulated stem cells (which is often the case with fat-derived) or enriched stem cell products (when MSC populations are expanded by culture in the laboratory). Then he looks at what the case requires. “Culture and expansion is necessary if it is deemed important to produce an abundant and homogenous stem cell preparation because of the low numbers of MSCs in the source material,” he noted, mentioning that only one in 100,000 of the nucleated cells (cells that have a nucleus—in blood these are usually white blood cells, as red blood cells have no nucleus) in bone marrow is an MSC, hence the need for culture/expansion.
Smith uses cultured bone-marrow-derived MSCs in his practice and reported that he has increased his standard dose to 20 million cells (at a concentration of 10 million cells/mL) with the option to increase this twofold for larger lesions, “because of the large loss of cells post-implantation and clinical outcome analysis has indicated better outcome with this large number.”
Smith summarized the techniques he uses to aspirate (both from the sternum and the tuber coxae--the bony prominence of the hip behind the flank) and administer bone-marrow-derived stem cells to treat tendon injuries. Some of the tips he included were to:
- Be sure the entire needle is visible on ultrasound to avoid inadvertent perforation of the deep surface of the tendon where cells would leak out.
- Inject stem cells into one to five sites, depending on the nature of the core lesion. An injury further along in healing will require more injection sites because the cells cannot spread as well through echogenic (more filled in) tissue.
- After administering MSCs, apply stable bandages to maintain the limb's temperature to maximize healing. “This is more important in cold climates, as distal limb temperature is then several degrees below core temperature and most cells are happiest at 37 degrees C (98.6 degrees F),” said Smith.
As is the practice at this peer-reviewed meeting, Smith disclosed that he was formerly a director and technical advisor of VetCell Bioscience Ltd and is currently a scientific advisor for Recellerate Inc.
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