Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells
Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells
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DOI：
10.1007/s12185-020-02916-8
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发表时间：
2020-06-22
影响因子：
2.1
通讯作者：
Miura, Yasuo
中科院分区：
文献类型：
--
作者：
Fujishiro, Aya;Iwasa, Masaki;Miura, Yasuo
维生素K2以menatetrenone的形式对骨质疏松症和血细胞减少症有临床益处。鉴于间充质-成骨细胞在造血调控中的主导作用，我们研究了甲烯雌酮是否改变人骨髓间充质基质/干细胞（BM-MSCs）的造血支持能力。甲烯雌酮上调BM-MSCs中纤维连接蛋白的表达，而不影响其增殖和分化能力。此外，BM-MSC的甲烯雌酮处理通过加速细胞周期增强了共培养物中CD 34（+）细胞群的产生。这种作用与VLA-4和纤连蛋白介导的细胞-细胞相互作用有关。细胞因子阵列和定量实时PCR分析支持了这一建议，其中幼稚和经甲烯雌酮处理的BM-MSC中造血相关可溶性因子的表达水平之间没有显著差异。在与经甲烯雌酮处理的BM-MSC共培养中的造血细胞的分析表明，与与未经处理的BM-MSC共培养中的造血细胞相比，它们包括显著更多的CD 34（+）CD 38（+）造血祖细胞和倾向于骨髓和巨核细胞谱系的细胞。值得注意的是，骨髓增生异常综合征衍生的细胞被诱导进行细胞凋亡时，与BM-MSCs共培养，这种效果增强了甲烯雌酮。总体而言，我们的研究结果表明，与menatetrenone的药理学治疗赋予BM-MSCs独特的造血支持能力，这可能有助于血细胞减少症的临床改善。
Vitamin K2 in the form of menatetrenone has clinical benefits for osteoporosis and cytopenia. Given the dominant role of mesenchymal-osteolineage cells in the regulation of hematopoiesis, we investigated whether menatetrenone alters the hematopoiesis-supportive capability of human bone marrow mesenchymal stromal/stem cells (BM-MSCs). Menatetrenone up-regulated fibronectin protein expression in BM-MSCs without affecting their proliferation and differentiation capabilities. In addition, menatetrenone treatment of BM-MSCs enhanced generation of the CD34(+)cell population in co-cultures through acceleration of the cell cycle. This effect was associated with cell-cell interactions mediated by VLA-4 and fibronectin. This proposal was supported by cytokine array and quantitative real-time PCR analyses, in which there were no significant differences between the expression levels of hematopoiesis-associated soluble factors in naive and menatetrenone-treated BM-MSCs. Profiling of hematopoietic cells in co-cultures with menatetrenone-treated BM-MSCs demonstrated that they included significantly more CD34(+)CD38(+)hematopoietic progenitor cells and cells skewed toward myeloid and megakaryocytic lineages than those in co-cultures with untreated BM-MSCs. Notably, myelodysplastic syndrome-derived cells were induced to undergo apoptosis when co-cultured with BM-MSCs, and this effect was enhanced by menatetrenone. Overall, our findings indicate that pharmacological treatment with menatetrenone bestows a unique hematopoiesis-supportive capability on BM-MSCs, which may contribute to the clinical improvement of cytopenia.