@article{oai:shiga-med.repo.nii.ac.jp:00003629, author = {藤城, 綾 and 岩佐, 磨佐紀 and 前川, 平 and 安藤, 朗 and FUJISHIRO, Aya and IWASA, Masaki and FUJII, Sumie and MAEKAWA, Taira and ANDOH, Akira and TOHYAMA, Kaoru and TAKAORI-KONDO, Akifumi and MIURA, Yasuo}, journal = {International journal of hematology}, month = {Jun}, note = {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 naïve 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., Journal Article}, title = {Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells.}, year = {2020} }