Allogeneic mesenchymal stem cells improve the wound healing process of sheep skin

Abstract

BackgroundSkin wound healing includes a system of biological processes, collectively restoring the integrity of the skin after injury. Healing by second intention refers to repair of large and deep wounds where the tissue edges cannot be approximated and substantial scarring is often observed. The objective of this study was to evaluate the effects of mesenchymal stem cells (MSCs) in second intention healing using a surgical wound model in sheep. MSCs are known to contribute to the inflammatory, proliferative, and remodeling phases of the skin regeneration process in rodent models, but data are lacking for large animal models. This study used three different approaches (clinical, histopathological, and molecular analysis) to assess the putative action of allogeneic MSCs at 15 and 42 days after lesion creation.ResultsAt 15 days post-lesion, the wounds treated with MSCs showed a higher degree of wound closure, a higher percentage of re-epithelialization, proliferation, neovascularization and increased contraction in comparison to a control group. At 42 days, the wounds treated with MSCs had more mature and denser cutaneous adnexa compared to the control group. The MSCs-treated group showed an absence of inflammation and expression of CD3+ and CD20+. Moreover, the mRNA expression of hair-keratine (hKER) was observed in the MSCs-treated group 15 days after wound creation and had increased significantly by 42 days post-wound creation. Collagen1 gene (Col1α1) expression was also greater in the MSCs-treated group compared to the control group at both days 15 and 42.ConclusionPeripheral blood-derived MSCs may improve the quality of wound healing both for superficial injuries and deep lesions. MSCs did not induce an inflammatory response and accelerated the appearance of granulation tissue, neovascularization, structural proteins, and skin adnexa.

The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review

“…Pitchford et al found, that MSCs/CFU-F were not found in mice PB post-mobilization with G-CSF, but when adding vascular endothelial growth factor and CXCR4-antagonist (Pitchford et al, 2009). Spaas et al systematically studied the isolation and culture methods, cell characteristics, and clinical safety of equine PB-MSCs, and applied them to many veterinary clinical studies, such as promoting cartilage repair, cutaneous wound healing, and healing of tendon and ligament lesions (Spaas et al, 2013;Beerts et al, 2017;Martinello et al, 2018;Broeckx et al, 2019a). Allogenic or xenogeneic MSCs banks, improving the mobilization and purification techniques, and shortening the culture cycle might effectively account for deficiencies in autologous MSCs, reduce the burden on both patients and treatment providers, and promote the development of singlestage procedures (Moroni and Fornasari, 2013;Pescador et al, 2017).…”

Locally Delivered Umbilical Cord Mesenchymal Stromal Cells Reduce Chronic Inflammation in Long-Term Nonhealing Wounds: A Randomized Study

“…The laboratory comparison of UCMSCSs with MSCs isolated from bone marrow according to morphology, expression of surface markers CD105, CD73, and CD90, and ability to differentiate into adipocytes, chondroblasts, and osteoblasts demonstrated their similarity in accordance with the minimal criteria proposed for MSCs by ISCT [20,21,32]. Preliminary animal studies have suggested that the infusion of MSCs from bone marrow and adipose tissue promotes healing of full-thickness wounds in mice [26,33], rats [34], rabbits [27], sheep [35]. Enhanced wound healing in diabetic mice was also observed after subcutaneous administration of human UCMSCs.…”

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

“…The sheep model has also been described for wound healing studies because it allows for the creation of relatively large and deep wounds to mimic the typical scenario of traumatic injuries like burn injuries or decubitus ulcers. Martinello et al (2018) used a sheep second intention wound healing model and showed how the intradermal and topical application of allogeneic MSCs led to a better re-epithelialization and dermal structure as compared to the control group at 42 days after wounding (Martinello et al, 2018). The identical model was recently used by Iacopetti et al (2020) to compare secondary intention healing of wounds, treated with a topical application of commercially available hyaluronic acid, Manuka honey or Acemannan gel (Iacopetti et al, 2020).…”