Abstract
Objective To assess the clinical value and safety of the application of allogeneic equine oral mucosa mesenchymal stromal cells (OM-MSCs) to wounds. Animals. 8 healthy adult horses without front limb skin lesions or musculoskeletal disease. Procedures. Stem cells were isolated from the oral mucosa of a donor horse. Horses were subjected to the creation of eight full-thickness cutaneous wounds, two on each distal forelimb (FL) and two on both sides of the thorax (TH). Each wound was subjected to one out of four treatments: no medication (T1), hyaluronic acid- (HA-) gel containing OM-MSC (T2), HA-gel containing OM-MSC secretome (T3), and HA-gel alone (T4). Gross macroscopic evaluation and laser digital photographic documentation were regularly performed to allow wound assessment including wound surface area. Full-thickness skin punch biopsy was performed at each site before wound induction (D0, normal skin) and after complete wound healing (D62, repaired skin). Results All wounds healed without adverse effect at D62. Distal limb wounds are slower to heal than body wounds. OM-MSC and its secretome have a positive impact on TH wound contraction. OM-MSC has a positive impact on the contraction and epithelialization of FL wounds. No significant difference between wound sites before and after treatment was noted at histological examination. Conclusion and Clinical Relevance. Using horse cells harvested from oral mucosa is a feasible technique to produce OM-MSC or its secretome. The gel produced by the combination of these biologic components with HA shows a positive impact when applied during the early stage of wound healing.
Highlights
Wound healing is a dynamic process that proceeds through a carefully orchestrated interaction of cellular and molecular events, which start whenever there is a break in tissue integrity
After 23 days, all TH wounds had nearly achieved their healing process, whereas FL wounds only started their decrease in surface area size. is faster healing process on the TH compared to the wound on an FL (23 days versus 60 days) is in agreement with previous results showing a slower contraction rate on the distal compared to the proximal part of the limb [25, 26]
In the first phase of healing, the presence of OM-Mesenchymal stromal cells (MSCs) or its secretome leads to amplification of the wound healing process. is hypothesis is in agreement with the assumption of Textor [20] observing a dramatic increase in the expression of COX-2 when MSCs are injected in equine wounds one week after creation. ese results are in concordance with previous data reporting that priming of MSCs by inflammatory signals is required to have a therapeutic effect [28]
Summary
Wound healing is a dynamic process that proceeds through a carefully orchestrated interaction of cellular and molecular events, which start whenever there is a break in tissue integrity. Current knowledge indicates that nonhealing wounds or development of EGT have many contributing factors, including reduced angiogenesis [3, 4], persistent secretion of growth factors leading to a fibroproliferative response [5], and an imbalance in collagen homeostasis [6] In horses, such fibroproliferative disorders [7] are responsible for poor healing in the distal limbs, limiting an athletic career and at the origin of expensive treatments. Ese cells can be isolated from various tissues and modulate wound healing through the release of several paracrine factors, enzymes, and immunomodulatory cytokines [21] In addition to these properties, they have shown the ability to release into the extracellular environment a number of vesicles containing multiple factors with therapeutic efficacy largely demonstrated in different animal models [22, 23]. In addition to these properties, they have shown the ability to release into the extracellular environment a number of vesicles containing multiple factors with therapeutic efficacy largely demonstrated in different animal models [22, 23]. ese lipids, nucleic acid, and proteins (growth factors, chemokines, cytokines, adhesion molecules, and proteases) secreted by the cell into the extracellular space are called the secretome
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