Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells
- 22 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in International Journal of Hematology
- Vol. 112 (3), 316-330
- https://doi.org/10.1007/s12185-020-02916-8
Abstract
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.Keywords
Funding Information
- Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province (18K08323)
- Takeda Science Foundation
- Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology in Japan (19K17856)
- Japanese Society of Hematology Research Grant
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