Keloid scarring remains a challenging clinical problem due to both resistance to treatment as well as high rates of recurrence. Research into possible treatments is also hindered by keloid scarring being a uniquely human phenomenon. Recent evidence supports a role for mesenchymal stem cells (MSC) as anti-fibrotic agents, possibly through paracrine signalling. The authors postulate that MSCs may also have an effect on keloid scarring. Keloid-derived fibroblasts (KF) were obtained from patients and cultured. These fibroblasts were then exposed to adipose tissue-derived stem cell (ASC) culture media (CM), containing cytokines which may have a paracrine effect on fibrosis. In addition, an established keloid implantation animal model was used to assess ASC-CM effect on scarring in vivo. Lastly, the authors identified cytokines and growth factors present in the ASC-CM using an antibody-based protein array. KF proliferation, migration and contractility were all significantly reduced in response to exposure to ASC-CM. In addition, expression of pro-fibrotic TGF-βs was significantly reduced. In the keloid implantation model, injection of ASC-CM into the keloid scarring significantly reduced keloid xenograft weight by over 20%. Histological analysis confirmed reductions in both inflammatory cells and vascularity as well as decreased collagen fibre thickness. The cytokine profile of the ASC-CM compared to control media demonstrated increased levels of a number of cytokines including a number of anti-fibrotic or pro-apoptotic factors. This study further contributes to the increasing body of evidence supporting a role for MSC / ASC as anti-fibrotic agents. Specifically, it demonstrates that ASCs produce cytokines which have a paracrine effect on keloid fibroblasts and can reduce keloid xenograft size in vivo. This suggests the possibility for use of ASCs in clinical treatment of keloid scars. Lastly, the increased expression of specific anti-fibrotic cytokines in ASC-CM may identify future therapeutic targets for treatment of keloid scars.
