One of the great mysteries surrounding the field of stem cell therapy is how the cells are distributed after being injected. Do they disperse evenly? Do they travel to the area where they’re needed? And how long do they stick around?
Using scintigraphy (a technique also used for bone scan), University of California (UC), Davis, researchers are studying different mesenchymal stem cell (MSC) administration techniques to determine which one results in the best distribution in the horse’s foot. And, thus far, intra-arterial injection is leading the pack. Mathieu Spriet, DVM, MS, Dipl. ACVR, ECVDI, associate professor of clinical diagnostic imaging at UC Davis’ School of Veterinary Medicine, presented his team’s results at the 2013 International Equine Conference on Laminitis and Diseases of the Foot, held Nov. 1-3 in West Palm Beach, Fla.
Although not studying stem cell distribution in regards to laminitis specifically, Spriet acknowledged that the team's findings might benefit those using mesenchymal stem cells (capable of differentiating into various cell types) to treat this devastating hoof disease. Currently, he said, veterinarians use intravenous (IV) regional limb perfusion or coronary band injection when administering MSC to treat laminitis. However, Spriet said these methods might result in suboptimal distribution to the pastern and foot.
So he and his team compared four methods of MSC administration in live horses:
- Intra-arterial (IA) injection through the median artery under general anesthesia and without applying a tourniquet to reduce the horse’s risk of developing arterial thrombosis (a dangerous blood clot);
- IV regional limb perfusion (IVRLP) through the lateral palmar digital vein (located on the outside of the horse’s fetlock) under general anesthesia and with a tourniquet;
- IVRLP through the lateral palmar digital vein under standing sedation and with a tourniquet; and
- Subcutaneous coronary band injection at three different sites.
The researchers administered approximately 35 million allogeneic (harvested from a different horse’s body) bone marrow-derived MSC to six healthy horses using each of the four methods. Spriet said they first performed the IA injection on one limb and IV with general anesthesia on other limb. Two months later they performed the IV under standing sedation on one limb and the coronary band injections on the other limb. The team took serial scintigraphic images up to 24 hours after each injection to measure stem cell uptake as well as persistence.
Spriet said findings included:
- With IA injection, the MSC travelled down to the foot and diffused evenly. “Not using a tourniquet allows blood flow to diffuse the cells, and there was no evidence of thrombosis,” he said. "Some of the cells are lost to the general circulation but at least half of them remained there initially."
- With IV under general anesthesia, the MSC travelled to the foot but distributed asymmetrically, with most remaining in the larger vessels close to the injection site.
- With IV under standing sedation, cells did not distribute properly and a large number were lost to the general circulation due to tourniquet failure. (On a standing horse, the tourniquet is not as efficient at obstructing blood flow through the veins due to the loading of the tendons, Spriet explained.)
- With coronary band injection, the MSC did not migrate within the hoof and were instead taken up by the lymphatic system.
- With all four methods, the researchers could still detect MSC 24 hours post-injection.
In conclusion, Spriet said, “Intra-arterial injection is the preferred technique for administration of MSC to the foot. It would be necessary to perform IVRLP through both the lateral and medial palmar digital veins in order to perfuse the entire foot.”
The only limitation to IA injection, he said, is the technique’s difficulty due to where the artery is located deep on the inside of the horse’s limb. Because this injection requires ultrasound guidance, its use is restricted to trained specialists.
His team is now assessing the effects of IA-injected MSC in horses that have foot lesions.
The study, "Scintigraphic comparison of intra-arterial injection and distal intravenous regional limb perfusion for administration of mesenchymal stem cells to the equine foot," was published in the October 2013 issue of the Equine Veterinary Journal.
Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.
