Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells.
Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells.
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DOI：
10.1038/srep22288
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发表时间：
2016-02-29
影响因子：
4.6
通讯作者：
Takahashi M
中科院分区：
文献类型：
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作者：
Maeda K;Enomoto A;Hara A;Asai N;Kobayashi T;Horinouchi A;Maruyama S;Ishikawa Y;Nishiyama T;Kiyoi H;Kato T;Ando K;Weng L;Mii S;Asai M;Mizutani Y;Watanabe O;Hirooka Y;Goto H;Takahashi M
培养的骨髓间充质基质细胞 (BM-MSC) 源自骨髓基质细胞或骨骼干细胞。尽管间充质干细胞已在临床医学中得到利用，但间充质干细胞特异性标记物的鉴定仍然有限。在这里，我们报告细胞表面和分泌蛋白 Meflin 在培养的间充质干细胞、成纤维细胞和周细胞中表达，但在其他类型的细胞（包括上皮细胞、内皮细胞和平滑肌细胞）中不表达。在体内，Meflin 由未成熟的成骨细胞和软骨细胞表达。此外，Meflin 存在于分布在整个骨髓中的基质细胞以及多个器官的周细胞和血管周围细胞上。 Meflin 维持培养的 MSC 的未分化状态，并在分化时下调，这与 Meflin 缺陷小鼠表现出成骨细胞数量增加和骨骼发育加速的观察结果一致。在骨骼和骨髓中，与 Sca-1 阴性脂肪成骨祖细胞相比，Meflin 在表达血小板衍生生长因子受体 α 和 Sca-1 的原始基质细胞中表达更高，从而为造血创造了利基。这些结果与 Meflin 缺陷小鼠的 BM 内克隆集落形成单位成纤维细胞数量的减少一致。这些初步数据表明 Meflin 是体内培养的 MSC 及其来源细胞的潜在标记物。
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo.