Wound healing, particularly of the lower limbs, is fraught with development of exuberant granulation tissue or chronicity in non-healing. It is believed that these problems are related to reduced angiogenesis, fibroproliferative responses elicited by persistent secretion of growth factors, and dysfunction of collagen homeostasis. In contrast, wounds of the oral cavity tend to heal quickly and without scarring, indicative of a population of stem cells and favorable cellular mediators.
French researchers evaluated a regenerative therapy using allogeneic mesenchymal stromal cells (MSCs) isolated from a tissue biopsy of the oral mucosa of the inner cheek of a donor horse, referred to as OM-MSC [Di Francesco, P.; Cajon, P.; Desterke, C.; et al. Effect of Allogeneic Oral Mucosa Mesenchymal Stromal Cells on Equine Wound Repair. Veterinary Medicine International Dec 2021; doi.org/10.1155/2021/5024905].
The double-blind, randomized trial used eight healthy adult horses ages 9-15 years with no limb lameness or skin disease or scars. The horses were confined in box stalls for 16 days, then allowed outdoor small paddocks for the remainder of the 90-day study. Four skin wounds were created by punch biopsies at two different body sites: two on the thorax behind the tip of the elbow and two on the dorsal aspect of the forelimb cannon bone. Then the wounds were treated for four days and dressed using non-adherent, permeable dressings that were changed on Days 2, 3 and 4. Dressings on the limb wounds were then changed every four days until Day 16. The thorax wounds had dressings removed on Day 6. No other medication was given to the horses throughout the study.
Tissue pieces of oral mucosal biopsies were prepared as an MSC suspension combined with hyaluronic acid (HA-gel). MSCs have immune modulating, anti-inflammatory, reparative and regenerative properties that are beneficial for healing of injured tissues. Each horse served as its own control: One wound was left untreated, one was treated with OM-MSC embedded in HA-gel, one was treated with OM-MSC secretome embedded in HA-gel, one was treated with only HA gel. (The MSC secretome contains lipids, nucleic acid, growth factors, chemokines, cytokines, proteases and adhesion molecules secreted by the stem cells into extracellular tissues.)
Scoring of the wounds ranged from score 0 to 4 using digital imagery and precise calculations with software. Measurements took into account the wound size increase or decrease, granulation of at least one wound edge, and wound size reduction with or without epithelialization.
Tissue biopsies—central and edge—of each wound were taken during wound creation and again on Day 62. The biopsies received scores of 0 to 4 for degree of epithelialization, granulation tissue, inflammatory cell infiltration and neo-vascularization.
Wound contraction takes longer in the forelimbs than the thorax, with thorax wounds 90% healed by 23 days while forelimb wounds only started to contract by then and did not heal until 60 days. Bandages were removed from the thorax by Day 6.
The authors note that bandages reduce oxygen tension and might exacerbate granulation tissue and slow healing of distal limb wounds.
By 11 days, the circumference and surface area decreased on thorax wounds treated with HA-gel containing OM-MSC or its secretome. There was no clinical difference nor was there a difference in histologic scoring between wound sites before and after treatment with the two stem cell preparations. The thoracic wounds healed with minimal or no scarring.
For the forelimb wounds, those treated with HA-gel alone healed the fastest by Day 62. No matter the treatment applied to distal limb wounds, some developed at least a little exuberant granulation tissue, perhaps due to the continuous 16 days of bandaging.
In conclusion, the authors reported: “During the early stage of healing, an HA-gel containing OM-MSC or its secretome induces a more rapid contraction profile in thoracic wounds.”
The gel containing stem cells but not the secretome had the greatest influence on wound contraction and epithelialization of the forelimb wounds.
There is a therapeutic window during the early stages of healing when you might augment the healing process by using oral stem cells and/or stem cell secretome in an HA-gel.