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.
© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
Publication Date: 2017-10-24 PubMed ID: 29063737PubMed Central: PMC5746157DOI: 10.1002/sctm.17-0071Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research focuses on the use of mesenchymal stem cell (MSC) therapy to improve the healing of distal extremity wounds in horses, discovering that direct injection of these cells into the wound area resulted in better healing outcomes.
Objectives and Methodology of the Study
- The study set out to understand the impact of direct treatment of wounds using allogeneic stem cells. The focus was on the gross, histologic, and transcriptional characteristics of the healing process.
- Three full-thickness cutaneous wounds were created on the distal forelimb of six healthy horses, thus making a total of six wounds per horse.
- Equine Mesenchymal Stem Cells (MSCs), derived from umbilical cord blood, were applied to each wound on the day following wound creation using four methods: injection of cells preconditioned in normal or low oxygen (normoxic or hypoxic) environments into wound margins, or use of normoxic or hypoxic-preconditioned cells placed within autologous fibrin gels and applied topically to the wound bed.
- Control wounds were treated with saline injection or blank fibrin gel.
Collection of Data and Findings
- Data were collected for six weeks and included measurements of wound surface area, thermography results, gene expression levels, and scores derived from histologic examination.
- The results showed that regardless of the method of delivery, MSC treatment was safe and improved histologic outcomes and wound area size.
- However, preconditioning the stem cells in a low-oxygen or hypoxic environment did not provide any additional benefits.
- Direct injection of the MSCs into the wound margins led to significant increases in the expression of two key wound healing markers, transforming growth factor beta and cyclooxygenase-2.
- From a histologic perspective, wounds that received MSC treatment were more likely to be classified as pro-healing than pro-inflammatory.
- The area of the wounds was also significantly affected by treatment: wounds where MSCs were injected were consistently smaller than those treated with gel or controls.
Conclusion
- The findings of the research suggest that MSC therapy could show promise in the treatment of distal extremity wounds in horses. The results were particularly positive when the cells were directly injected into the wound margins.
Cite This Article
APA
Textor JA, Clark KC, Walker NJ, Aristizobal FA, Kol A, LeJeune SS, Bledsoe A, Davidyan A, Gray SN, Bohannon-Worsley LK, Woolard KD, Borjesson DL.
(2017).
Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses.
Stem Cells Transl Med, 7(1), 98-108.
https://doi.org/10.1002/sctm.17-0071 Publication
Researcher Affiliations
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Veterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Veterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Veterinary Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
- Department of Pathology, Microbiology, Immunology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
MeSH Terms
- Animals
- Cell Hypoxia
- Cyclooxygenase 2 / analysis
- Female
- Fetal Blood / cytology
- Horses
- Male
- Mesenchymal Stem Cell Transplantation
- Mesenchymal Stem Cells / cytology
- Skin / injuries
- Transforming Growth Factor beta / analysis
- Wound Healing / physiology
- Wounds and Injuries / therapy
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