Bone marrow adipose tissue-derived stem cell factor mediates metabolic regulation of hematopoiesis

Zhang, Zengdi; Huang, Zan; Ong, Brianna; Sahu, Chinmayi S; Zeng, Hu; Ruan, Hai Bin

doi:10.3324/haematol.2018.205856

Cited by 52 publications

(38 citation statements)

References 72 publications

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“…Inactivity increases MAT, which can impair hematopoiesis by occupying space and/or through paracrine action 58 . Tight reciprocal relationship between MAT and hematopoiesis 59 , 60 support that adipocytes are negative regulators of hematopoietic stem cell 55 . Low EPO has also been shown to favor adipogenesis 61 .…”

Section: Discussionmentioning

confidence: 99%

Six degrees head-down tilt bed rest caused low-grade hemolysis: a prospective randomized clinical trial

et al. 2021

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This study aimed to measure hemolysis before, during and after 60 days of the ground-based spaceflight analog bed rest and the effect of a nutritional intervention through a prospective randomized clinical trial. Twenty male participants were hospitalized for 88 days comprised of 14 days of ambulatory baseline, 60 days of 6° head-down tilt bed rest and 14 days of reambulation. Ten participants each received a control diet or daily polyphenol associated with omega-3, vitamin E, and selenium supplements. The primary outcome was endogenous carbon monoxide (CO) elimination measured by gas chromatography. Hemolysis was also measured with serial bilirubin, iron, transferrin saturation blood levels and serial 3-day stool collections were used to measure urobilinoid excretion using photometry. Total hemoglobin mass (tHb) was measured using CO-rebreathing. CO elimination increased after 5, 11, 30, and 57 days of bed rest: +289 ppb (95% CI 101–477 ppb; p = 0.004), +253 ppb (78–427 ppb; p = 0.007), +193 ppb (89–298 ppb; p = 0.001) and +858 ppb (670–1046 ppb; p < 0.000), respectively, compared to baseline. Bilirubin increased after 20 and 49 days of bed rest +0.8 mg/l (p = 0.013) and +1.1 mg/l (p = 0.012), respectively; and iron increased after 20 days of bed rest +10.5 µg/dl (p = 0.032). The nutritional intervention did not change CO elimination. THb was lower after 60 days of bed rest −0.9 g/kg (p = 0.001). Bed rest enhanced hemolysis as measured through all three by-products of heme oxygenase. Ongoing enhanced hemolysis over 60 days contributed to a 10% decrease in tHb mass. Modulation of red blood cell control towards increased hemolysis may be an important mechanism causing anemia in astronauts.

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Section: Discussionmentioning

confidence: 99%

Six degrees head-down tilt bed rest caused low-grade hemolysis: a prospective randomized clinical trial

et al. 2021

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“…Mesenchymal stromal cells’ secretion of SCF has been instead associated with appropriate homing of HSPCs ( Horwitz et al, 2011 ). Mainly secreted by BM adipocytes and Lepr+ stromal cells, studies on mice have proven that SCF is essential for HSPC regeneration as well as hematopoiesis and cell homeostasis, particularly in conditions of obesity and aging ( Zhang et al, 2019 ; Zhou et al, 2017 ). Inhibition of the appropriate interactions between SCF receptor and ligand has shown to enhance HSPC clearance, confirming the chemokine role in HSPCs’ self-renewal ( Czechowicz et al, 2007 ).…”

Section: Mesenchymal Stromal Cells’ Hematopoietic Supportmentioning

confidence: 99%

Role of ex vivo Expanded Mesenchymal Stromal Cells in Determining Hematopoietic Stem Cell Transplantation Outcome

Crippa

Santi

Berti

et al. 2021

Front. Cell Dev. Biol.

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Overall, the human organism requires the production of ∼1 trillion new blood cells per day. Such goal is achieved via hematopoiesis occurring within the bone marrow (BM) under the tight regulation of hematopoietic stem and progenitor cell (HSPC) homeostasis made by the BM microenvironment. The BM niche is defined by the close interactions of HSPCs and non-hematopoietic cells of different origin, which control the maintenance of HSPCs and orchestrate hematopoiesis in response to the body’s requirements. The activity of the BM niche is regulated by specific signaling pathways in physiological conditions and in case of stress, including the one induced by the HSPC transplantation (HSCT) procedures. HSCT is the curative option for several hematological and non-hematological diseases, despite being associated with early and late complications, mainly due to a low level of HSPC engraftment, impaired hematopoietic recovery, immune-mediated graft rejection, and graft-versus-host disease (GvHD) in case of allogenic transplant. Mesenchymal stromal cells (MSCs) are key elements of the BM niche, regulating HSPC homeostasis by direct contact and secreting several paracrine factors. In this review, we will explore the several mechanisms through which MSCs impact on the supportive activity of the BM niche and regulate HSPC homeostasis. We will further discuss how the growing understanding of such mechanisms have impacted, under a clinical point of view, on the transplantation field. In more recent years, these results have instructed the design of clinical trials to ameliorate the outcome of HSCT, especially in the allogenic setting, and when low doses of HSPCs were available for transplantation.

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“…Perivascular stromal cells and endothelial cells are crucial components of the HSC niche, which is highlighted by the fact that both cell types secrete SCF [24]. Moreover, BM adipocytes are also a major supplier of SCF [27] and a study in mice with an adipocyte-specific knockout revealed that MAT-derived SCF is essential for hematopoiesis both under steady state and metabolic stress conditions [28].…”

Section: Our Bones Are Full Of Fat-but Why?mentioning

confidence: 99%

Adipocytes in hematopoiesis and acute leukemia: friends, enemies, or innocent bystanders?

Zinngrebe¹,

Debatin²,

Fischer‐Posovszky³

2020

Leukemia

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The bone marrow is home to well-balanced normal hematopoiesis, but also the stage of leukemia’s crime. Marrow adipose tissue (MAT) is a unique and versatile component of the bone marrow niche. While the importance of MAT for bone health has long been recognized, its complex role in hematopoiesis has only recently gained attention. In this review article we summarize recent conceptual advances in the field of MAT research and how these developments impact our understanding of MAT regulation of hematopoiesis. Elucidating routes of interaction and regulation between MAT and cells of the hematopoietic system are essential to pinpoint vulnerable processes resulting in malignant transformation. The concept of white adipose tissue contributing to cancer development and progression on the cellular, metabolic, and systemic level is generally accepted. The role of MAT in malignant hematopoiesis, however, is controversial. MAT is very sensitive to changes in the patient’s metabolic status hampering a clear definition of its role in different clinical situations. Here, we discuss future directions for leukemia research in the context of metabolism-induced modifications of MAT and other adipose tissues and how this might impact on leukemia cell survival, proliferation, and antileukemic therapy.

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Bone marrow adipose tissue-derived stem cell factor mediates metabolic regulation of hematopoiesis

Cited by 52 publications

References 72 publications

Six degrees head-down tilt bed rest caused low-grade hemolysis: a prospective randomized clinical trial

Six degrees head-down tilt bed rest caused low-grade hemolysis: a prospective randomized clinical trial

Role of ex vivo Expanded Mesenchymal Stromal Cells in Determining Hematopoietic Stem Cell Transplantation Outcome

Adipocytes in hematopoiesis and acute leukemia: friends, enemies, or innocent bystanders?

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