Alessio Nicola, Özcan Servet, Tatsumi Kazuki, Murat Ayşegül, Peluso Gianfranco, Dezawa Mari, Galderisi Umberto
a Department of Experimental Medicine , Biotechnology and Molecular Biology Section, Second University of Naples , Naples , Italy.
b Genome and Stem Cell Center (GENKOK), Erciyes University , Kayseri , Turkey.
Cell Cycle. 2017 Jan 2;16(1):33-44. doi: 10.1080/15384101.2016.1211215. Epub 2016 Jul 27.
Mesenchymal stromal cells (MSCs) are a heterogeneous population, which contain several cell phenotypes: mesenchymal stem cells, progenitor cells, fibroblasts and other type of cells. Previously, we identified unique stem cells that we named multilineage-differentiating stress enduring (Muse) cells as one to several percent of MSCs of the bone marrow, adipose tissue and dermis. Among different cell populations in MSCs, Muse cells, positive for pluripotent surface marker SSEA-3, may represent cells responsible for pluripotent-like property of MSCs, since they express pluripotency genes, able to differentiated into triploblastic cells from a single cells and are self-renewable. MSCs release biologically active factors that have profound effects on local cellular dynamics. A thorough examination of MSC secretome seems essential for understanding the physiological functions exerted by these cells in our organism and also for rational cellular therapy design. In this setting, studies on secretome of Muse cells may shed light on pathways that are associated with their specific features. Our findings evidenced that secretomes of MSCs and Muse cells contain factors that regulate extracellular matrix remodeling, ox-redox activities and immune system. Muse cells appear to secrete factors that may preserve their stem cell features, allow survival under stress conditions and may contribute to their immunomodulation capacity. In detail, the proteins belonging to protein kinase A signaling, FXR/RXR activation and LXR/RXR activation pathways may play a role in regulation of Muse stem cell features. These last 2 pathways together with proteins associated with antigen presentation pathway and coagulation system may play a role in immunomodulation.
间充质基质细胞（MSCs）是一个异质群体，包含多种细胞表型：间充质干细胞、祖细胞、成纤维细胞和其他类型的细胞。此前，我们在骨髓、脂肪组织和真皮的MSCs中鉴定出了独特的干细胞，我们将其命名为多谱系分化应激耐受（Muse）细胞，占比为1%至2%。在MSCs的不同细胞群体中，多能表面标志物SSEA-3呈阳性的Muse细胞可能代表了赋予MSCs多能样特性的细胞，因为它们表达多能性基因，能够从单个细胞分化为三胚层细胞，并且具有自我更新能力。MSCs释放具有生物活性的因子，这些因子对局部细胞动态有深远影响。全面研究MSCs的分泌组对于理解这些细胞在我们机体中发挥的生理功能以及合理设计细胞治疗方案似乎至关重要。在这种情况下，对Muse细胞分泌组的研究可能会揭示与其特定特征相关的途径。我们的研究结果表明，MSCs和Muse细胞的分泌组包含调节细胞外基质重塑、氧化还原活性和免疫系统的因子。Muse细胞似乎分泌一些因子，这些因子可能维持其干细胞特征，使其在应激条件下存活，并可能有助于其免疫调节能力。具体而言，属于蛋白激酶A信号通路、FXR/RXR激活和LXR/RXR激活途径的蛋白质可能在调节Muse干细胞特征中发挥作用。最后这两条途径以及与抗原呈递途径和凝血系统相关的蛋白质可能在免疫调节中发挥作用。
