Adipose-derived stem cells in wound healing: recent results in vitro and in vivo

Introduction Chronic wounds represent a major problem in medicine today as their incidence is continuously increasing due to an ageing population and a rise in the incidence of underlying diseases. Cutaneous wound healing is a complex biological process. Chronic wounds are characterised by a prolonged inflammation, persistent infections, formation of drugresistant microbial biofilms and the inability of dermal and/or epidermal cells to respond to regenerative stimuli. As conventional treatment strategies often fail, innovative therapies have been investigated over the last decade, including stem cell-based therapies. After the initial use of embryonic stem cells, the focus has been set on autologous mesenchymal stem cells over the past years. They can be isolated in large amounts from various tissues and hold no ethical concerns. A promising and cost-effective source of autologous mesenchymal stem cells is subcutaneous adipose tissue. Recent in vitro and in vivo studies have shown that adiposederived stem cells have a positive impact on wound healing, as they are attracted to the wound site and influence regeneration processes via paracrine mechanisms. They are pluripotent and secrete a variety of growth factors. The aim of this critical review was to discuss adiposederived stem cells in wound healing. Conclusion Mesenchymal stem cells-derived from adipose tissue are a promising alternative to embryonic or bone marrow-derived stem cells in the therapy of chronic wounds. Because the use of adipose-derived stem cells in wound healing applications is still limited by a lack of clinical data, further studies have to pave the way for their routine clinical application. Introduction Due to demographic changes the number of patients with multimorbidity is continuously increasing in western countries. One of the associated disorders is the chronic wound. This includes a rise in the incidence of impaired wound healing, causing a reduced patients’ quality of life and rising health care costs. Conventional therapies of chronic wounds are increasingly reaching their limits, motivating the search for alternative treatment options, including stem cell-based therapies1. This paper discusses the recent in vitro and in vivo results of adipose-derived stem cells (ASCs) in wound healing. Physiological wound healing Wound healing is a complex biological process consisting of the four different but partially overlying steps coagulation, inflammation, formation of granulation tissue (proliferative phase) and remodelling or scar formation. After injury, initiation of a bloodclotting cascade prevents excessive bleeding and provides temporary protection of the wound area. During this process platelet-derived growth factor and transforming growth factors A1 and 2 (TGF-A1 and TGF-2) are released, causing attraction of inflammatory cells such as leukocytes and macrophages. Within a few days after injury, apoptosis of inflammatory cells occurs. Anti-inflammatory cytokines such as TGF-A1 and Interleukin (IL) 1 as well as bioactive lipids are assumed to be involved in this process (Figure 1). In the following proliferative phase, production of growth factors and activation of dermal and epidermal cells lead to new tissue formation. Endothelial progenitor cells, which are essential for physiological wound healing, are mobilised by nitric oxide, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP9). Formation of extra-cellular matrix (ECM)rich tissue occurs in response to stromal cell-derived factor (SDF)-1 and insulin-like growth factor (IGF). In the last step of wound healing, matrix remodelling and/or scar formation through cellular migration, proliferation and angiogenic induction is initiated by TGF-A, MMPs and tumour necrosis factor (TNF)2. Impaired wound healing A chronic wound is defined as a wound that does not heal in a certain period of time in spite of appropriate therapy. However, the exact-time point is in discussion. Most authors refer to a chronic wound as a wound that exists for more than three months3. Impaired wound healing is associated with senescence, ischaemia and bacterial colonisation. Wound chronification is caused by local factors such as infection, venous insufficiency, mechanical trauma, * Corresponding author Email: [email protected] 1 Institute for Research in Operative Medicine, University of Witten/Herdecke, Ostmerheimer Str. 200, D-51109 Cologne, Germany 2 Department of Trauma and Orthopaedic Surgery, Cologne-Merheim Medical Center, University of Witten/Herdecke, Cologne, Germany