Maria Cecilia Hospital, GVM Care & Research, 48,033 Cotignola (RA), Italy.
University of Ferrara, Department of Medical Sciences, via Fossato di Mortara 70, 44,121 Ferrara, Italy.
Cells. 2019 Jul 16;8(7):729. doi: 10.3390/cells8070729.
Diabetic foot ulcers (DFUs) are lesions that involve loss of epithelium and dermis, sometimes involving deep structures, compartments, and bones. The aim of this work is to investigate the innate regenerative properties of dermal tissue around ulcers by the identification and analysis of resident dermal stem cells (DSCs). Dermal samples were taken at the edge of DFUs, and genes related to the wound healing process were analyzed by the real-time PCR array. The DSCs were isolated and analyzed by immunofluorescence, flow cytometry, and real-time PCR array to define their stemness properties. The gene expression profile of dermal tissue showed a dysregulation in growth factors, metalloproteinases, collagens, and integrins involved in the wound healing process. In the basal condition, diabetic DSCs adhered on the culture plate with spindle-shaped fibroblast-like morphology. They were positive to the mesenchymal stem cells markers CD44, CD73, CD90, and CD105, but negative for the hematopoietic markers CD14, CD34, CD45, and HLA-DR. In diabetic DSCs, the transcription of genes related to self-renewal and cell division were equivalent to that in normal DSCs. However, the expression of , 2, 1, 1, and 2 was downregulated compared with that of normal DSCs. These genes are also related to cell cycle progression and stem cell maintenance. Further investigation will improve the understanding of the molecular mechanisms by which these genes together govern cell proliferation, revealing new strategies useful for future treatment of DFUs.
糖尿病足溃疡(DFUs)是一种涉及上皮和真皮丧失的病变,有时还涉及深部结构、腔室和骨骼。本研究旨在通过鉴定和分析溃疡周围的真皮组织固有再生特性来研究这一问题。从 DFU 的边缘采集真皮样本,并通过实时 PCR 阵列分析与伤口愈合过程相关的基因。通过免疫荧光、流式细胞术和实时 PCR 阵列分离和分析 DSCs,以定义其干性特征。真皮组织的基因表达谱显示,参与伤口愈合过程的生长因子、金属蛋白酶、胶原和整合素存在失调。在基础条件下,糖尿病 DSCs 以梭形成纤维细胞样形态附着在培养板上。它们对间充质干细胞标志物 CD44、CD73、CD90 和 CD105 呈阳性,但对造血标志物 CD14、CD34、CD45 和 HLA-DR 呈阴性。在糖尿病 DSCs 中,与自我更新和细胞分裂相关的基因转录与正常 DSCs 相当。然而,与正常 DSCs 相比, 2、1、1、和 2 的表达下调。这些基因也与细胞周期进展和干细胞维持有关。进一步的研究将提高对这些基因共同控制细胞增殖的分子机制的理解,为未来治疗 DFUs 提供新的策略。