Oral Stem Cells Help Heal Wounds in Horses

Wounds often leave scars, hairless patches, and other unsightly blemishes. Traumatic wounds to the legs may result in proud flesh or excessive granulation tissue that can be difficult to manage. In a recent study, stem cells derived from oral tissues positively influenced the healing of wounds.^*

Exploring the use of stem cell therapy for wounds in horses has important clinical implications. Nonhealing wounds or those characterized by excessive granulation tissue may delay or limit a horse’s athletic career and are expensive to treat and manage. Until now, stem cells have been used primarily in the management of musculoskeletal injuries, such as tendon lesions.

“Wound healing involves a carefully orchestrated series of events involving growth factors, blood vessel formation, and a balanced production of fibrous tissue and collagen. Stem cells, such as those derived from oral tissues such as the cheek, exert immunomodulatory, anti-inflammatory, reparative, and regenerative properties,” explained Kathleen Crandell, Ph.D., a nutritionist for Kentucky Equine Research.

Further, an increasing body of evidence suggests that stem cells also secrete a variety of paracrine factors, enzymes, and immunomodulatory cytokines known as the secretome. These molecules, released into the extracellular tissues in “extracellular vesicles,” may also facilitate wound healing and decrease reliance on using the entire stem cell.

In this study, oral mucosal stem cells were harvested from a tissue biopsy obtained from the inner cheek. Stem cells were isolated and multiplied in the laboratory. A hyaluronic acid-based (HA) gel was created that contained either the stem cells themselves or stem cells with secretome. This HA gel, either alone, with the stem cells, or with just the secretome, were applied to wounds on the thorax or front limbs of eight healthy horses. The HA-gel treatments were applied the day after wound creation. Wound healing was assessed visually and microscopically for 62 days.

“Wounds on the thorax healed more quickly than wounds on the lower limbs. Full healing of thoracic wounds was achieved by day 26, whereas full healing of wounds on the limbs was not noted until day 60,” Crandell said.

A significant decrease in the circumference and surface area was identified for thoracic wounds treated with HA-gel containing the stem cells or secretome. Only the gel containing stem cells (not the secretome) appeared to influence wound healing on the forelimbs.

“We conclude from these observations that a beneficial effect can be obtained with these regenerative medicine treatments when used at an early stage of the wound-healing process,” wrote the researchers.

They suggested that a “therapeutic window” exists. If oral mucosal stem cells or the secretome are applied in the first phase of healing, amplification of the wound healing process may occur. In fact, the wounds on the forelimbs actually increased in size until day 23 before beginning to contract.

Mild proud flesh was observed on the forelimb wounds in this study. The researchers felt this was due to bandaging the wounds for 16 days. Excess bandaging is a risk factor for proud flesh formation. Treatment was not implemented, and the researchers stated that all wounds healed without complications.

“Given the complex nature of wound healing, high incidence of complications, and prolonged healing periods, every step should be taken to support healthy skin,” Crandell emphasized.

“Dietary omega-3 fatty acids possess anti-inflammatory properties, can attenuate systemic inflammation, and may decrease susceptibility to wound infections. High-quality omega-3 fatty acid supplements support wound healing and benefit other features of skin and coat health,” she said.

EO-3 is a palatable marine-derived source of the long-chain omega-3 fatty acids DHA and EPA.

^*Di Francesco, P., P. Cajon, C. Desterke, M.-F.P. Lepage, J.-J. Lataillade, T. Kadri, and O. Lepage. 2021. Effect of allogeneic oral mucosa mesenchymal stromal cells on equine wound repair. Veterinary Medicine International:5024905.