Hematopoietic Stem Cell Niche: Role in Normal and Malignant Hematopoiesis

Bydlowski, Sérgio Paulo; Levy, Débora; Ruiz, Jorge M.L.; JulianaPereira,

doi:10.5772/55508

Cited by 2 publications

(1 citation statement)

References 46 publications

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“…HSCs could move from the BM through circulation and home back to their stem cell niche at the inner surface of the bone cavity as a response to environmental cues including growth factors, cytokines, ligands, oxygen content, chemotactic, and calcium gradients (Aksoz, Turan, Albayrak, & Kocabas, 2018; Kocabas et al, 2015; Simsek et al, 2010; Yucel & Kocabas, 2018). This is referred as mobilization and homing (Bydlowski, Levy, Ruiz, & Pereira, 2013; Ratajczak & Suszynska, 2016). For successful transplantation of HSCs, homing must be followed by engraftment (Wolf, 1974), which is adhesion and retention of HSCs in their specialized niche in the BM.…”

Section: Discussionmentioning

confidence: 99%

Temporal modulation of calcium sensing in hematopoietic stem cells is crucial for proper stem cell expansion and engraftment

Uslu

Albayrak

Kocabaş

2020

Journal Cellular Physiology

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Hematopoietic stem cells (HSCs) are known to reside in a bone marrow (BM) niche, which is associated with relatively higher calcium content. HSCs sense and respond to calcium changes. However, how calcium‐sensing components modulate HSC function and expansion is largely unknown. We investigated temporal modulation of calcium sensing and Ca2+ homeostasis during ex vivo HSC culture and in vivo. Murine BM‐HSCs, human BM, and umbilical cord blood (UCB) mononuclear cells (MNCs) were treated with store‐operated calcium entry (SOCE) inhibitors SKF 96365 hydrochloride (abbreviated as SKF) and 2‐aminoethoxydiphenyl borate (2‐APB). Besides, K+ channel inhibitor TEA chloride (abbreviated as TEA) was used to compare the relationship between calcium‐activated potassium channel activities. Seven days of SKF treatment induced mouse and human ex vivo BM‐HSC expansion as well as UCB‐derived primitive HSC expansion. SKF treatment induced the surface expression of CaSR, CXCR4, and adhesion molecules on human hematopoietic stem and progenitor cells. HSCs expanded with SKF successfully differentiated into blood lineages in recipient animals and demonstrated a higher repopulation capability. Furthermore, modulation of SOCE in the BM‐induced HSC content and differentially altered niche‐related gene expression profile in vivo. Intriguingly, treatments with SOCE inhibitors SKF and 2‐APB boosted the mouse BM mesenchymal stem cell (MSC) and human adipose‐derived MSCs proliferation, whereas they did not affect the endothelial cell proliferation. These findings suggest that temporal modulation of calcium sensing is crucial in expansion and maintenance of murine HSCs, human HSCs, and mouse BM‐MSCs function.

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Section: Discussionmentioning

confidence: 99%

Temporal modulation of calcium sensing in hematopoietic stem cells is crucial for proper stem cell expansion and engraftment

Uslu

Albayrak

Kocabaş

2020

Journal Cellular Physiology

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Endothelial progenitor cells in multiple myeloma neovascularization: a brick to the wall

2017

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Multiple myeloma (MM) is characterized by the clonal expansion of plasma cells in the bone marrow that leads to events such as bone destruction, anaemia and renal failure. Despite the several therapeutic options available, there is still no effective cure, and the standard survival is up to 4 years. The evolution from the asymptomatic stage of monoclonal gammopathy of undetermined significance to MM and the progression of the disease itself are related to cellular and molecular alterations in the bone marrow microenvironment, including the development of the vasculature. Post-natal vasculogenesis is characterized by the recruitment to the tumour vasculature of bone marrow progenitors, known as endothelial progenitor cells (EPCs), which incorporate newly forming blood vessels and differentiate into endothelial cells. Several processes related to EPCs, such as recruitment, mobilization, adhesion and differentiation, are tightly controlled by cells and molecules in the bone marrow microenvironment. In this review, the bone marrow microenvironment and the mechanisms associated to the development of the neovasculature promoted by EPCs are discussed in detail in both a non-pathological scenario and in MM. The latest developments in therapy targeting the vasculature and EPCs in MM are also highlighted. The identification and characterization of the pathways relevant to the complex setting of MM are of utter importance to identify not only biomarkers for an early diagnosis and disease progression monitoring, but also to reveal intervention targets for more effective therapy directed to cancer cells and the endothelial mediators relevant to neovasculature development.

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Hematopoietic Stem Cell Niche: Role in Normal and Malignant Hematopoiesis

Cited by 2 publications

References 46 publications

Temporal modulation of calcium sensing in hematopoietic stem cells is crucial for proper stem cell expansion and engraftment

Temporal modulation of calcium sensing in hematopoietic stem cells is crucial for proper stem cell expansion and engraftment

Endothelial progenitor cells in multiple myeloma neovascularization: a brick to the wall

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