The effects of topical mesenchymal stem cell transplantation in canine experimental cutaneous wounds

Abstract

Background - Adult stem cells have been widely investigated in bioengineering approaches for tissue repair therapy. We evaluated the clinical value and safety of the application of cultured bone marrow-derived allogenic mesenchymal stem cells (MSCs) for treating skin wounds in a canine model. Hypothesis - Topical allogenic MSC transplantation can accelerate the closure of experimental full-thickness cutaneous wounds and attenuate local inflammation. Animals - Adult healthy beagle dogs (n = 10; 3-6 years old; 7.2-13.1 kg) were studied. Methods - Full-thickness skin wounds were created on the dorsum of healthy beagles, and allogenic MSCs were injected intradermally. The rate of wound closure and the degree of collagen production were analysed histologically using haematoxylin and eosin staining and trichrome staining. The degree of cellular proliferation and angiogenesis was evaluated by immunocytochemistry using proliferating cell nuclear antigen-, vimentin- and alpha-smooth muscle actin-specific antibodies. Local mRNA expression levels of interleukin-2, interferon-gamma, basic fibroblast growth factor and matrix metalloproteinase-2 were evaluated by RT-PCR. Results - Compared with the vehicle-treated wounds, MSC-treated wounds showed more rapid wound closure and increased collagen synthesis, cellular proliferation and angiogenesis. Moreover, MSC-treated wounds showed decreased expression of pro-inflammatory cytokines (interleukin-2 and interferon-gamma) and wound healing-related factors (basic fibroblast growth factor and matrix metalloproteinase-2). Conclusion and clinical importance - Topical transplantation of MSCs results in paracrine effects on cellular proliferation and angiogenesis, as well as modulation of local mRNA expression of several factors related to cutaneous wound healing.