Abstract

Limb wounds on horses are often slow to heal and are prone to developing exuberant granulation tissue (EGT) and close primarily through epithelialization, which results in a cosmetically inferior and non-durable repair. In contrast, wounds on the body heal rapidly and primarily through contraction and rarely develop EGT. Intravenous (IV) multipotent mesenchymal stromal cells (MSCs) are promising. They home and engraft to cutaneous wounds and promote healing in laboratory animals, but this has not been demonstrated in horses. Furthermore, the clinical safety of administering >1.00 × 108 allogeneic MSCs IV to a horse has not been determined. A proof-of-principle pilot project was performed with two horses that were administered 1.02 × 108 fluorescently labeled allogeneic cord blood-derived MSCs (CB-MSCs) following wound creation on the forelimb and thorax. Wounds and contralateral non-wounded skin were sequentially biopsied on days 0, 1, 2, 7, 14, and 33 and evaluated with confocal microscopy to determine presence of homing and engraftment. Results confirmed preferential homing and engraftment to wounds with persistence of CB-MSCs at 33 days following wound creation, without clinically adverse reactions to the infusion. The absence of overt adverse reactions allows further studies to determine effects of IV CB-MSCs on equine wound healing.

Highlights

  • Cutaneous wounds are common in horses and often must heal by second intention

  • We have previously shown that almost all testis stem cells exposed to AAV2 were successfully transduced with enhanced green fluorescent protein (eGFP) [39] and stably expressed the eGFP transgene for several years in vivo [40]

  • One horse had symptoms of mild colic prior to injection of the CB-mesenchymal stromal cells (MSCs) that was attributed to anesthesia and because her vital signs remained normal the cord blood-derived MSCs (CB-MSCs) were administered

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Summary

Introduction

Cutaneous wounds are common in horses and often must heal by second intention. Limb wounds have prolonged low-grade inflammation which causes slower healing and less contraction, and this in turn promotes development of exuberant granulation tissue (EGT) and a less durable and less cosmetic repair [1,2]. Cells 2020, 9, 1162 develop these fibroproliferative disorders, making the horse a good animal model for studying keloids and hypertrophic scars in humans [3]. Multipotent mesenchymal stromal cells (MSCs) have been investigated as ancillary therapy for complicated cutaneous healing and keloid treatment in humans [4,5,6,7]. Experimental studies examining the effects of multipotent cells on equine cutaneous wounds are limited [12,13,14]

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