ABSTRACT
Non-healing wounds are a major complication of diabetes that can lead to limb amputation and disability in patients. The normal process of wound repair progresses through well-defined stages including hemostasis, inflammation, proliferative, and remodeling, which may be impaired in diabetic wounds. In recent years, it has been reported that keratinocytes, a major cell type in human skin, play a key role in the healing process of wounds. In this overview, firstly, a summary of the wound healing process is provided and the role of keratinocytes in wound healing is briefly reviewed. Then, a set of evidence about the impaired keratinocytes activities in diabetic wounds and clinical trials focused mainly on improving keratinocytes in the context of diabetic wound therapeutics are summarized. Keratinocytes can produce signaling molecules that act in a paracrine and autocrine way, causing pleiotropic effects on various cell types. The affected cells respond to keratinocytes by creating several signaling molecules, which also adjust keratinocyte activation through wound healing. In diabetic wounds, disruption of various biological mechanisms leads to dysfunction of keratinocytes including impaired migration, adhesion, and proliferation. The function of abnormal keratinocytes can lead to poor diabetic wound healing. Taken together, clarification of molecular and functional disturbances of keratinocyte cells and applying them in diabetic wounds can contribute to enhanced treatment of diabetic wounds. Based on the location of keratinocytes in the epidermis and the central role of keratinocytes in the diabetic wound healing process, applying keratinocytes has great potential for the treatment of diabetic burn wounds.
ABSTRACT
Introduction: Diabetic burn wounds and ulcers are significant complications of diabetic patients. The aim of this study is to investigate the use of platelet rich-plasma (PRP) and/or keratinocyte-like cells (KLCs) in diabetic thermal wound rat model and to evaluate EGF, FGF-2, TGF-ß1, COL1α2, MCP-1 and VEGF-α as wound healing markers at gene expression level. Method: In this study, we used adipose tissue as the source of mesenchymal stem cells (MSCs) and differentiated MSCs into KLCs. KLCs were characterized and transferred to the burn areas on the dorsum of streptozotocine (STZ)-induced diabetic rats. We prepared PRP from rat blood and evaluated its effect alone or in combination with KLCs. On 3rd, 7th, 10th and 14th days after treatment, wound areas were measured and biopsy samples were excised from the wound areas of the KLCs and/or PRP-treated and untreated diabetic rats to analyze gene expression levels of wound healing markers by qPCR. Results: We observed that, wound contraction started earlier in the PRP and/or KLCs-treated groups in comparison to the control group. However, PRP and KLCs when applied in combination showed additive affect in wound healing. In all groups treated with KLCs and/or PRP, the gene expression levels of evaluated growth factors and COL1α2 increased, while MCP-1 levels decreased when compared to the untreated diabetic rats. In addition, the most prominent difference in qPCR results belongs to combined PRP and KLCs-treated group. Conclusion: We demonstrated that applying PRP and KLCs in combination has a greater potential for treatment of diabetic burn wounds.
