Cell regenerative therapy is a modern solution for difficult-to-heal wounds. Keratinocytes, the most common cell type in the skin, are difficult to obtain without the creation of another wound. Stem cell differentiation towards keratinocytes is a challenging process, and it is difficult to reproduce in chemically defined media. Nevertheless, a co-culture of keratinocytes with stem cells usually achieves efficient differentiation. This systematic review aims to identify the secretions of normal human keratinocytes reported in the literature and correlate them with the differentiation process. An online search revealed 338 references, of which 100 met the selection criteria. A total of 80 different keratinocyte secretions were reported, which can be grouped mainly into cytokines, growth factors, and antimicrobial peptides. The growth-factor group mostly affects stem cell differentiation into keratinocytes, especially epidermal growth factor and members of the transforming growth factor family. Nevertheless, the reported secretions reflected the nature of the involved studies, as most of them focused on keratinocyte interaction with inflammation. This review highlights the secretory function of keratinocytes, as well as the need for intense investigation to characterize these secretions and evaluate their regenerative capacities.

Risk adjustment and mortality prediction models are central in optimising care and for benchmarking purposes. In the burn setting, the Baux score and its derivatives have been the mainstay for predictions of mortality from burns. Other well-known measures to predict mortality stem from the ICU setting, where, for example, the Simplified Acute Physiology Score (SAPS 3) models have been found to be instrumental. Other attempts to further improve the prediction of outcome have been based on the following variables at admission: Sequential Organ Failure Assessment (_aSOFA) score, determinations of _aLactate or Neutrophil to Lymphocyte Ratio (_aNLR). The aim of the present study was to examine if estimated mortality rate (EMR, SAPS 3), _aSOFA, _aLactate, and _aNLR can, either alone or in conjunction with the others, improve the mortality prediction beyond that of the effects of age and percentage total body surface area (TBSA%) burned among patients with severe burns who need critical care. This is a retrospective, explorative, single centre, registry study based on prospectively gathered data. The study included 222 patients with median (25th–75th centiles) age of 55.0 (38.0 to 69.0) years, TBSA% burned was 24.5 (13.0 to 37.2) and crude mortality was 17%. As anticipated highest predicting power was obtained with age and TBSA% with an AUC at 0.906 (95% CI 0.857 to 0.955) as compared with EMR, _aSOFA, _aLactate and _aNLR. The largest effect was seen thereafter by adding _aLactate to the model, increasing AUC to 0.938 (0.898 to 0.979) (p < 0.001). Whereafter, adding EMR, _aSOFA, and _aNLR, separately or in combinations, only marginally improved the prediction power. This study shows that the prediction model with age and TBSA% may be improved by adding _aLactate, despite the fact that _aLactate levels were only moderately increased. Thereafter, adding EMR, _aSOFA or _aNLR only marginally affected the mortality prediction.

Wound healing is regulated by complex crosstalk between keratinocytes and other cell types, including stem cells. In this study, a 7-day direct co-culture model of human keratinocytes and adipose-derived stem cells (ADSCs) was proposed to study the interaction between the two cell types, in order to identify regulators of ADSCs differentiation toward the epidermal lineage. As major mediators of cell communication, miRNome and proteome profiles in cell lysates of cultured human keratinocytes and ADSCs were explored through experimental and computational analyses. GeneChip^® miRNA microarray, identified 378 differentially expressed miRNAs; of these, 114 miRNAs were upregulated and 264 miRNAs were downregulated in keratinocytes. According to miRNA target prediction databases and the Expression Atlas database, 109 skin-related genes were obtained. Pathway enrichment analysis revealed 14 pathways including vesicle-mediated transport, signaling by interleukin, and others. Proteome profiling showed a significant upregulation of the epidermal growth factor (EGF) and Interleukin 1-alpha (IL-1α) compared to ADSCs. Integrated analysis through cross-matching the differentially expressed miRNA and proteins suggested two potential pathways for regulations of epidermal differentiation; the first is EGF-based through the downregulation of miR-485-5p and miR-6765-5p and/or the upregulation of miR-4459. The second is mediated by IL-1α overexpression through four isomers of miR-30-5p and miR-181a-5p.