Equivalent Effects of Topically-Delivered Adipose-Derived Stem Cells and Dermal Fibroblasts in the Ischemic Rabbit Ear Model for Chronic Wounds

Background: Mesenchymal stem cells (MSC) have garnered considerable attention in plastic surgery. Via proliferation/differentiation or the elaboration of paracrine factors, MSC and their adipose-derived stem cell counterparts (ADSC) have been suggested to stimulate cutaneous wound healing. Previous reports have been limited by a lack of appropriate controls and the lack of a clinically-relevant context or ability to extrapolate to human wound healing. Objectives: The authors qualitatively and quantitatively evaluate the ability of ADSC to improve wound healing in an ischemic variant of their well-established rabbit ear wound model. Methods: To incorporate ischemia, a major pathophysiologic factor in human chronic wounds, into our model, two of the three main arteries to the rabbit ear were ligated before wounding. Green fluorescent protein (GFP) labeled ADSC or rabbit dermal fibroblasts (RDF) were then applied to wounds and histologic parameters of healing quantified. Results: At Postoperative Day (POD) 1, both cell types were present in a uniform distribution across wounds and positive for the proliferation marker Ki-67. By POD 7 and continuing through POD 10, ADSC and RDF contributed similarly to the accumulation of stratified "neogranulation" across the wound bed. No statistically-significant differences were observed between ADSC and RDF in terms of this positive effect on granulation (P=.2-.3 for comparison of mean granulation tissue gaps and areas). Conclusions: ADSC and RDF can be delivered topically to wounds, resulting in a high level of engraftment in the ischemic background. Cellular wound therapy holds promise for chronic wound healing as well as other antiscarring therapies, but further studies are warranted before full clinical translation.