Kočí Zuzana, Turnovcová Karolína, Dubský Michal, Baranovičová Lenka, Holáň Vladimír, Chudíčková Milada, Syková Eva, Kubinová Sárka
Department of Neuroscience, Institute of Experimental Medicine, Academy of Science, Prague, Czech Republic; Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
Cell Biochem Funct. 2014 Oct;32(7):597-604. doi: 10.1002/cbf.3056. Epub 2014 Sep 23.
Adipose tissue is an abundant source of autologous adult stem cells that may bring new therapeutic perspectives on the treatment of diabetes and its complications. It is unclear whether adipose tissue-derived stromal cells (ASCs) of diabetic patients, constantly influenced by hyperglycaemia, have the same properties as non-diabetic controls. As an alternative source of ASCs, adipose tissue from distal limbs of diabetic patients with critical ischemia was isolated. ASCs were characterized in terms of cell surface markers, multilineage differentiation and the expression of vascular endothelial growth factor (VEGFA), chemokine-related genes and compared with non-diabetic controls. Flow cytometry analysis confirmed mesenchymal phenotypes in both diabetic and non-diabetic ASCs. Nevertheless, 40% of diabetic and 20% of non-diabetic ASC samples displayed high expressions of fibroblast marker, which inversely correlated with the expression of CD105. In diabetic patients, significantly decreased expression of VEGFA and chemokine receptor CXCR4 was found in fibroblast-positive ASCs, compared with their fibroblast-negative counterparts. Reduced osteogenic differentiation and the downregulation of chemokine CXCL12 were found in fibroblast-negative diabetic ASCs. Both diabetic and non-diabetic ASCs were differentiated into adipocytes and chondrocytes and did not reveal islet-like cell differentiation. According to this study, adipose tissue from distal limbs of diabetic patients is not satisfactory as an autologous ASC source. Hyperglycaemic milieu as well as other metabolic disorders linked to diabetes may have an influence on endogenous stem cell properties. The present study investigated the feasibility of autologous stem cell therapy in diabetic patients. ASCs isolated from the ischemic limb of diabetic patients were found to be less potent when compared phenotypically and functionally to control non-diabetic counterparts with no signs of limb ischemia. High expression of fibroblast markers associated with reduced expression of VEGFA as well as reduced osteogenic differentiation may have an impact on the effectiveness of autologous cell therapies in diabetic patients.
脂肪组织是自体成体干细胞的丰富来源，这可能为糖尿病及其并发症的治疗带来新的治疗前景。目前尚不清楚长期受高血糖影响的糖尿病患者的脂肪组织来源基质细胞（ASC）是否具有与非糖尿病对照组相同的特性。作为ASC的替代来源，分离了患有严重缺血的糖尿病患者远端肢体的脂肪组织。对ASC进行了细胞表面标志物、多向分化以及血管内皮生长因子（VEGFA）、趋化因子相关基因表达方面的特征分析，并与非糖尿病对照组进行了比较。流式细胞术分析证实糖尿病和非糖尿病ASC均具有间充质表型。然而，40%的糖尿病ASC样本和20%的非糖尿病ASC样本显示成纤维细胞标志物高表达，这与CD105的表达呈负相关。在糖尿病患者中，与成纤维细胞阴性的ASC相比，成纤维细胞阳性的ASC中VEGFA和趋化因子受体CXCR4的表达显著降低。在成纤维细胞阴性的糖尿病ASC中发现成骨分化减少以及趋化因子CXCL12下调。糖尿病和非糖尿病ASC均可分化为脂肪细胞和软骨细胞，但未显示出胰岛样细胞分化。根据这项研究，糖尿病患者远端肢体的脂肪组织作为自体ASC来源并不理想。高血糖环境以及与糖尿病相关的其他代谢紊乱可能会对内源性干细胞特性产生影响。本研究调查了糖尿病患者自体干细胞治疗的可行性。与无肢体缺血迹象的非糖尿病对照相比，从糖尿病患者缺血肢体分离的ASC在表型和功能上效力较低。与VEGFA表达降低以及成骨分化减少相关的成纤维细胞标志物高表达可能会影响糖尿病患者自体细胞治疗的效果。
