Bone marrow‐derived mesenchymal stem cells propagate immunosuppressive/anti‐inflammatory macrophages in cell‐to‐cell contact‐independent and ‐dependent manners under hypoxic culture
Bone marrow‐derived mesenchymal stem cells propagate immunosuppressive/anti‐inflammatory macrophages in cell‐to‐cell contact‐independent and ‐dependent manners under hypoxic culture
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DOI：
10.1016/j.yexcr.2017.07.014
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发表时间：
2017-09
影响因子：
3.7
通讯作者：
Naoki Takizawa;N. Okubo;M. Kamo;N. Chosa;T. Mikami;Keita Suzuki;Seiji Yokota;Miho Ibi;M. Ohtsuka;Masayuki Taira;T. Yaegashi;A. Ishisaki;S. Kyakumoto
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文献类型：
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作者：
Naoki Takizawa;N. Okubo;M. Kamo;N. Chosa;T. Mikami;Keita Suzuki;Seiji Yokota;Miho Ibi;M. Ohtsuka;Masayuki Taira;T. Yaegashi;A. Ishisaki;S. Kyakumoto
免疫抑制/抗炎巨噬细胞（Mφ），即表达典型的M 2-Mφs标志物CD 206和抗炎细胞因子白细胞介素（IL）-10的M2-Mφ，是治疗炎症性疾病的有利工具。在这里，我们证明了在缺氧条件下，骨髓来源的谱系阳性（Lin+）血细胞通过与骨髓来源的间充质干细胞（MSC）合作增殖并分化为M2-Mφ：MSC不仅通过MSC分泌的巨噬细胞集落刺激因子的增殖作用促进未分化的M2-Mφs、前M2-Mφs的增殖，而且通过与pre-M2-M φ的细胞间接触促进pre-M2-Mφ的M2-Mφ极化。有趣的是，细胞间粘附分子（ICAM）-1受体/淋巴细胞功能相关抗原（LFA）-1的Rwj 50271抑制剂可部分抑制Lin+血细胞中CD 206的表达，但VCAM-1受体/VLA-4抑制剂BIO 5192则不能，提示通过前M2-Mφs上的LFA-1和MSC上的ICAM-1的细胞与细胞粘附被认为促进了M2-Mφ极化。因此，骨髓来源的Lin+血细胞与MSCs在低氧条件下组成的共培养体系是大量M2-Mφ的有益供应者，可用于临床炎症性疾病的治疗。
Immunosuppressive/anti-inflammatory macrophage (Mφ), M2-Mφ that expressed the typical M2-Mφs marker, CD206, and anti-inflammatory cytokine, interleukin (IL)-10, is beneficial and expected tool for the cytotherapy against inflammatory diseases. Here, we demonstrated that bone marrow-derived lineage-positive (Lin+) blood cells proliferated and differentiated into M2-Mφs by cooperation with the bone marrow-derived mesenchymal stem cells (MSCs) under hypoxic condition: MSCs not only promoted proliferation of undifferentiated M2-Mφs, pre-M2-Mφs, in the Lin+ fractionviaa proliferative effect of the MSCs-secreted macrophage colony-stimulating factor, but also promoted M2-Mφ polarization of the pre-M2-Mφs through cell-to-cell contact with the pre-M2-Mφs. Intriguingly, an inhibitor for intercellular adhesion molecule (ICAM)-1 receptor/lymphocyte function-associated antigen (LFA)-1, Rwj50271, partially suppressed expression of CD206 in the Lin+ blood cells but an inhibitor for VCAM-1 receptor/VLA-4, BIO5192, did not, suggesting that the cell-to-cell adhesion through LFA-1 on pre-M2-Mφs and ICAM-1 on MSCs was supposed to promoted the M2-Mφ polarization.Thus, the co-culture system consisting of bone marrow-derived Lin+ blood cells and MSCs under hypoxic condition was a beneficial supplier of a number of M2-Mφs, which could be clinically applicable to inflammatory diseases.