Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses

Abstract

Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full‐thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord‐blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic‐ or (b) hypoxic‐preconditioned cells injected into wound margins, or (c) normoxic‐ or (d) hypoxic‐preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel‐treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic‐preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase‐2 expression at week 1. Histologically, significantly more MSC‐treated wounds were categorized as pro‐healing than pro‐inflammatory. Wound area was significantly affected by treatment: MSC‐injected wounds were consistently smaller than gel‐treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. stem cells translational medicine 2018;7:98–108

Effects of acellular equine amniotic allografts on the healing of experimentally induced full‐thickness distal limb wounds in horses

“…This outcome was not anticipated by the authors because it has been reported that occlusive dressings potentially decrease the risk for wound infection . Moreover, bandage changes in previous equine distal limb wound healing studies ranged from one to three times per week, and no evidence of wound infection was reported during these trials . The exact cause of infection in this study remains unknown.…”

“…[69][70][71] Moreover, bandage changes in previous equine distal limb wound healing studies ranged from one to three times per week, and no evidence of wound infection was reported during these trials. [6][7][8][9][10][11][12][13] The exact cause of infection in this study remains unknown. An additional flaw in histologic processing further eliminated a control wound, reducing our total number of wounds to be examined from 32 to 28.…”

“…5 Current strategies to manage wounds seek to enhance the environment and the inflammatory response to promote appropriate wound healing. [6][7][8][9][10][11][12][13][14] Therapeutic options include administration of regenerative biological products, treatment with extracorporeal shockwave, and application of specialized wound dressings and ointments during specific stages of the wound healing process. [6][7][8][9][10][11][12][13][14] However, additional research is required to improve the treatment of extensive and/or chronic distal limb wounds in horses.…”

A Regenerative Approach to Canine Osteoarthritis Using Allogeneic, Adipose-Derived Mesenchymal Stem Cells. Safety Results of a Long-Term Follow-Up

“…The potential use of allogeneic MSCs for the treatment of various diseases has also been piloted, including humans and horses, for instance, for indications such as cardiac damage post-myocardial infarction and wound healing (26,27). However, whilst long-term safety data is still very sparse, evidence is now emerging on a convincing safety profile for the use of allogeneic MSCs in cardiac regeneration (28) and autoimmune disease in man (29) as well as in osteoarthritis in horses (30).…”

Impact of Nanocapsules on Red Blood Cells Interplay Jointly Assessed by Optical Tweezers and Microscopy

“…Nowadays, there are numerous delivery systems such as: natural biological vehicles (such as bacteria and viruses [1,2], various cell types including red blood cells (RBCs) [3][4][5], immune cells [6,7], stem cells [8][9][10][11] and manufactured carriers (liposomes [12], micelle [13], polymeric capsules [14][15][16][17], polymeric complexes [18][19][20][21]). Polymeric nanocapsules (NCs) are a promising system of natural carriers for targeted drug delivery because of their low cytotoxicity, shell flexibility, and high in vivo stability [22][23][24][25][26].…”