Nasal Polyp-Derived Mesenchymal Stromal Cells Exhibit Lack of Immune-Associated Molecules and High Levels of Stem/Progenitor Cells Markers.
Nasal Polyp-Derived Mesenchymal Stromal Cells Exhibit Lack of Immune-Associated Molecules and High Levels of Stem/Progenitor Cells Markers.
复制标题
鼻息肉衍生的间充质基质细胞表现出缺乏免疫相关的分子和高水平的茎/祖细胞标记。
DOI：
10.3389/fimmu.2017.00039
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发表时间：
2017
影响因子：
7.3
通讯作者：
Gregorio LC
中科院分区：
文献类型：
--
作者：
de Oliveira PW;Pezato R;Agudelo JS;Perez-Novo CA;Berghe WV;Câmara NO;de Almeida DC;Gregorio LC
间充质干细胞（MSC）被认为是成体祖干细胞，并已在许多组织中进行了研究。在这种情况下，鼻息肉组织的微环境中有几个炎症细胞，但它们的基质室仍然很少阐明。因此，我们从鼻息肉Polyp-MSCs（PO-MSCs）中分离出MSCs，并将其分子特征和基因表达模式与骨髓来源的MSCs（BM-MSCs）进行比较。最初，分离、培养PO-MSC和BM-MSC，并进行形态学、分化、表型、免疫抑制和基因表达测定。与BM-MSC相比，PO-MSC显示出正常的形态和相似的成骨/成脂分化潜力，但其免疫表型显示缺乏免疫相关分子（例如，CD 117、HLA-DR、PDL-1和PDL-2），其与较低的免疫调节能力有关，例如（i）抑制淋巴细胞增殖和（ii）调节性T细胞扩增。此外，我们在PO-MSCs中检测到与BM-MSCs相比不同的基因表达谱。PO-MSC表达更高水平的祖干细胞特异性标志物（例如，CD 133和ABCB 1），而BM-MSC显示细胞因子和生长因子（例如，FGF 10、KDR和GDF 6）。基因本体分析表明，PO-MSC中差异表达的基因与基质重塑过程和己糖、葡萄糖转运有关。对于BM-MSCs，高表达的基因与行为、血管生成、血管形态发生、细胞-细胞信号传导和对外部刺激的反应调节相关。因此，这些结果表明，PO-MSC，虽然与BM-MSC共享相似的方面，表达不同的分子谱，这可能与鼻息肉组织的发展有关。
Mesenchymal stromal cells (MSCs) are considered adult progenitor stem cells and have been studied in a multitude of tissues. In this context, the microenvironment of nasal polyp tissue has several inflammatory cells, but their stroma compartment remains little elucidated. Hence, we isolated MSCs from nasal polyps Polyp-MSCs (PO-MSCs) and compared their molecular features and gene expression pattern with bone marrow-derived MSCs (BM-MSCs). Initially, both PO-MSCs and BM-MSCs were isolated, cultivated, and submitted to morphologic, differentiation, phenotypic, immunosuppressive, and gene expression assays. Compared to BM-MSCs, PO-MSCs showed normal morphology and similar osteogenic/adipogenic differentiation potential, but their immunophenotyping showed lack of immune-associated molecules (e.g., CD117, HLA-DR, PDL-1, and PDL-2), which was linked with less immunoregulatory abilities such as (i) inhibition of lymphocytes proliferation and (ii) regulatory T cell expansion. Furthermore, we detected in the PO-MSCs a distinct gene expression profile in comparison with BM-MSCs. PO-MSC expressed higher levels of progenitor stem cells specific markers (e.g., CD133 and ABCB1), while BM-MSCs showed elevated expression of cytokines and growth factors (e.g., FGF10, KDR, and GDF6). The gene ontology analysis showed that the differentially modulated genes in PO-MSC were related with matrix remodeling process and hexose and glucose transport. For BM-MSCs, the highly expressed genes were associated with behavior, angiogenesis, blood vessel morphogenesis, cell–cell signaling, and regulation of response to external stimulus. Thus, these results suggest that PO-MSCs, while sharing similar aspects with BM-MSCs, express a different profile of molecules, which presumably can be implicated in the development of nasal polyp tissue.