Trivanović Drenka, Nikolić Srdjan, Krstić Jelena, Jauković Aleksandra, Mojsilović Slavko, Ilić Vesna, Okić-Djordjević Ivana, Santibanez Juan Francisco, Jovčić Gordana, Bugarski Diana
Laboratory for Experimental Hematology and Stem Cells, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
Cell Biol Int. 2014 Feb;38(2):254-65. doi: 10.1002/cbin.10198. Epub 2013 Nov 15.
Adipose tissue is an attractive source of mesenchymal stem/stromal cells (MSCs) with potential applications in reconstructive plastic surgery and regenerative medicine. The aim of this study was to characterise human adipose tissue MSCs (ASCs) derived from healthy individuals and cancer patients and to compare their interactions with tumour cells. ASCs were isolated from adipose tissue of healthy donors, breast cancer-adjacent adipose tissue of breast cancer patients and tumour-adjacent adipose tissue of non-breast cancer patients. Their proliferation, differentiation, immunophenotype and gene expression were assessed and effects on the proliferation of human breast cancer cell line MCF-7 compared. ASCs from all sources exhibited similar morphology, proliferative and differentiation potential, showing the characteristic pattern of mesenchymal surface markers expression (CD90, CD105, CD44H, CD73) and the lack of HLA-DR and hematopoietic markers (CD11a, CD33, CD45, Glycophorin-CD235a), but uneven expression of CD34. ASCs also shared a common positive gene expression of HLA-DR, HLA-A, IL-6, TGF-β and HIF-1, but were negative for HLA-G, while the expression levels of Cox-2 and IDO-1 varied. All ASCs significantly stimulated the proliferation of MCF-7 tumour cells in direct mixed co-cultures and transwell system, although their conditioned media displayed antiproliferative activity. Data obtained showed that ASCs with similar characteristics are easily isolated from various donors and sites of origin, although ASCs could both suppress and favour tumour cells growth, emphasising the importance of cellular context within the microenvironment and pointing to the significance of safety studies to exclude any potential clinical risk of their application in regenerative medicine.
脂肪组织是间充质干/基质细胞(MSCs)的一个有吸引力的来源,在整形重建外科和再生医学中具有潜在应用价值。本研究的目的是对来自健康个体和癌症患者的人脂肪组织间充质干细胞(ASCs)进行特性分析,并比较它们与肿瘤细胞的相互作用。从健康供体的脂肪组织、乳腺癌患者的乳腺癌旁脂肪组织以及非乳腺癌患者的肿瘤旁脂肪组织中分离出ASCs。评估了它们的增殖、分化、免疫表型和基因表达,并比较了它们对人乳腺癌细胞系MCF-7增殖的影响。所有来源的ASCs均表现出相似的形态、增殖和分化潜能,呈现间充质表面标志物表达(CD90、CD105、CD44H、CD73)的特征模式,且缺乏HLA-DR和造血标志物(CD11a、CD33、CD45、血型糖蛋白-CD235a),但CD34表达不均。ASCs还具有共同的HLA-DR、HLA-A、IL-6、TGF-β和HIF-1阳性基因表达,但HLA-G为阴性,而Cox-2和IDO-1的表达水平有所不同。在直接混合共培养和Transwell系统中,所有ASCs均显著刺激MCF-7肿瘤细胞的增殖,尽管它们的条件培养基显示出抗增殖活性。获得的数据表明,具有相似特征的ASCs很容易从不同供体和来源部位分离出来,尽管ASCs既能抑制也能促进肿瘤细胞生长,这强调了微环境中细胞背景的重要性,并指出了安全性研究对于排除其在再生医学中应用的任何潜在临床风险的重要性。