Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells

Fujishiro, Aya; Iwasa, Masaki; Fujii, Satoshi; Maekawa, Taira; Andoh, Akira; Tohyama, Kaoru; Takaori‐Kondo, Akifumi; Miura, Yasuo

doi:10.1007/s12185-020-02916-8

Cited by 5 publications

(1 citation statement)

References 53 publications

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“…In vitro evidence suggests dichotomous effects of VK2 in leukaemia cells [ 147 ] and that it causes suppression of cMYC [ 148 ] while improving haematopoiesis and promoting anti-apoptosis of normal erythroid progenitors and differentiation of myeloid progenitors [ 149 ]. The pro-apoptotic effects of co-culture of bone marrow mesenchymal stromal/stem cells (BM-MSCs) with MDS-derived cells were enhanced by MK-4 [ 150 ]. VK2 may thus offer potential as an adjunctive anti-cancer therapy in this cohort, especially for elderly patients who cannot tolerate intensive chemotherapy and stem cell transplantation.…”

Section: Potential Therapeutic Benefitsmentioning

confidence: 99%

Vitamin K2 in Health and Disease: A Clinical Perspective

Zhang,

O’Connor,

Sheridan

et al. 2024

Foods

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Vitamins are essential organic compounds that vary widely in chemical structure and are vital in small quantities for numerous biochemical and biological functions. They are critical for metabolism, growth, development and maintaining overall health. Vitamins are categorised into two groups: hydrophilic and lipophilic. Vitamin K (VK), a lipophilic vitamin, occurs naturally in two primary forms: phylloquinone (VK1), found in green leafy vegetables and algae, and Menaquinones (VK2), present in certain fermented and animal foods and widely formulated in VK supplements. This review explores the possible factors contributing to VK deficiency, including dietary influences, and discusses the pharmacological and therapeutic potential of supplementary VK2, examining recent global clinical studies on its role in treating diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis, cardiovascular disease, chronic kidney disease, diabetes, neurodegenerative disorders and cancers. The analysis includes a review of published articles from multiple databases, including Scopus, PubMed, Google Scholar, ISI Web of Science and CNKI, focusing on human studies. The findings indicate that VK2 is a versatile vitamin essential for human health and that a broadly positive correlation exists between VK2 supplementation and improved health outcomes. However, clinical data are somewhat inconsistent, highlighting the need for further detailed research into VK2′s metabolic processes, biomarker validation, dose–response relationships, bioavailability and safety. Establishing a Recommended Daily Intake for VK2 could significantly enhance global health.

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Section: Potential Therapeutic Benefitsmentioning

confidence: 99%

Vitamin K2 in Health and Disease: A Clinical Perspective

Zhang,

O’Connor,

Sheridan

et al. 2024

Foods

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Lenalidomide and pomalidomide modulate hematopoietic cell expansion and differentiation in the presence of MSC

Fujii,

Miura

2024

Int J Hematol

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Cytopenia is a well-documented complication in the treatment of hematological malignancies with lenalidomide and pomalidomide. Although prior studies have highlighted direct effects on hematopoietic cells to explain this adverse effect, the involvement of hematopoietic-supportive stroma remains less understood. This study examined the effects of lenalidomide/pomalidomide on the expansion and differentiation of human CD34+ hematopoietic stem/progenitor cells (HSPCs) in vitro, in co-culture with human bone-marrow mesenchymal stromal/stem cells (MSCs). Our findings indicate that lenalidomide/pomalidomide increases the population of immature CD34+CD38− cells while decreasing the number of mature CD34+CD38+ cells, suggesting a mechanism that inhibits early HSPC maturation. This effect persisted across myeloid, megakaryocytic, and erythroid lineages, with MSCs playing a key role in preserving immature progenitors and inhibiting their differentiation. Furthermore, in myeloid differentiation assays augmented by granulocyte-colony stimulating factor, lenalidomide/pomalidomide not only enhanced the presence of CD34+ cells with mature myeloid markers such as CD11b but also reduced the populations lacking CD34 yet positive for these markers, irrespective of MSC presence. Thus, while MSCs support the presence of these immature cell populations, they simultaneously inhibit their maturation. This finding provides novel mechanistic insights into lenalidomide- and pomalidomide-induced cytopenia, and could guide therapeutic strategies for its mitigation.

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Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies

Streuer

Jann

et al. 2023

Nat Commun

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Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling. We further confirm these results in vivo using a bone marrow niche-dependent MN xenograft model in female NSG mice, in which we additionally demonstrate an enforced reduction of dominant clones as well as significant attenuation of disease expansion and normalization of spleen sizes. Overall, these results lay out a strong pre-clinical rationale for efficacy of combination treatment of 5-AZA with PXS-5505 especially for anemic MN.

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Menatetrenone facilitates hematopoietic cell generation in a manner that is dependent on human bone marrow mesenchymal stromal/stem cells

Cited by 5 publications

References 53 publications

Vitamin K2 in Health and Disease: A Clinical Perspective

Vitamin K2 in Health and Disease: A Clinical Perspective

Lenalidomide and pomalidomide modulate hematopoietic cell expansion and differentiation in the presence of MSC

Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies

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