Poloni Antonella, Maurizi Giulia, Anastasi Sara, Mondini Eleonora, Mattiucci Domenico, Discepoli Giancarlo, Tiberi Fabiola, Mancini Stefania, Partelli Stefano, Maurizi Angela, Cinti Saverio, Olivieri Attilio, Leoni Pietro
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Clinica di Ematologia, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy.
Exp Hematol. 2015 Feb;43(2):137-46. doi: 10.1016/j.exphem.2014.10.003. Epub 2014 Oct 24.
The process of cellular differentiation in terminally differentiated cells is thought to be irreversible, and these cells are thought to be incapable of differentiating into distinct cell lineages. Our previous study showed that mature adipocytes represent an alternative source of mesenchymal stem cells. Here, results showed the capacity of mature adipocytes to differentiate into endothelial-like cells, using the ability of these cells to revert into an immature phase without any relievable chromosomal alterations. Mature adipocytes were isolated from human omental and subcutaneous fat and were dedifferentiated in vitro. The resulting cells were subcultivated for endothelial differentiation and were analyzed for their expression of specific genes and proteins. Endothelial-like cells were harvested from the differentiation medium and were traditionally cultured to evaluate the endothelial markers and the karyotype. Cells cultured in specific medium formed tube-like structures and expressed several endothelial marker genes and proteins. The endothelial-like cells expressed significantly higher levels of vascular endothelium growth factor receptor 2, vascular endothelial cadherin, Von Willebrand factor, and CD133 than the untreated cells. These cells were positively stained for CD31 and vascular endothelial cadherin, markers of mature endothelial cells. Moreover, the low-density lipoprotein-uptake assay demonstrated a functionally endothelial differentiation of these cells. When these cells were harvested and reseeded in basal medium, they lost the endothelial markers and reacquired the typical mesenchymal stem cell markers and the ability to expand in a short time period. Moreover, karyotype analysis showed that these cells reverted into an immature phase without any karyotype alterations. In conclusion, the results showed that adipocytes exhibited a great plasticity toward the endothelial lineage, suggesting their possible use in cell therapy applications for vascular disease.
终末分化细胞中的细胞分化过程被认为是不可逆的，并且这些细胞被认为无法分化为不同的细胞谱系。我们之前的研究表明，成熟脂肪细胞是间充质干细胞的另一种来源。在此，结果显示了成熟脂肪细胞分化为内皮样细胞的能力，利用这些细胞在无任何可缓解的染色体改变的情况下恢复到未成熟阶段的能力。从人网膜和皮下脂肪中分离出成熟脂肪细胞，并在体外进行去分化。将所得细胞传代培养以进行内皮分化，并分析其特定基因和蛋白质的表达。从分化培养基中收获内皮样细胞，并进行传统培养以评估内皮标志物和核型。在特定培养基中培养的细胞形成管状结构，并表达几种内皮标志物基因和蛋白质。内皮样细胞表达的血管内皮生长因子受体2、血管内皮钙黏蛋白、血管性血友病因子和CD133水平明显高于未处理的细胞。这些细胞对成熟内皮细胞的标志物CD31和血管内皮钙黏蛋白呈阳性染色。此外，低密度脂蛋白摄取试验证明了这些细胞在功能上的内皮分化。当这些细胞被收获并重新接种在基础培养基中时，它们失去了内皮标志物，重新获得了典型的间充质干细胞标志物以及在短时间内扩增的能力。此外，核型分析表明这些细胞恢复到未成熟阶段且无任何核型改变。总之，结果表明脂肪细胞对内皮谱系表现出很大的可塑性，表明它们可能用于血管疾病的细胞治疗应用。
