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

Jamie A. Textor, Kaitlin C. Clark, Naomi J. Walker, Fabio A. Aristizobal, Amir Kol, Sonia S Le jeune, Andrea Bledsoe, Arik Davidyan, Sarah N. Gray, Laurie K. Bohannon-Worsley, Kevin D Woolard, Dori L Borjesson

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)98-108
Number of pages11
JournalStem cells translational medicine
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • Animal models
  • Cord blood
  • Hypoxia
  • Mesenchymal stem cells
  • Tissue regeneration

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Textor, J. A., Clark, K. C., Walker, N. J., Aristizobal, F. A., Kol, A., Le jeune, S. S., Bledsoe, A., Davidyan, A., Gray, S. N., Bohannon-Worsley, L. K., Woolard, K. D., & Borjesson, D. L. (2018). Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses. Stem cells translational medicine, 7(1), 98-108. https://doi.org/10.1002/sctm.17-0071