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Nature Jan 2014Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their niches,... (Review)
Review
Niches are local tissue microenvironments that maintain and regulate stem cells. Haematopoiesis provides a model for understanding mammalian stem cells and their niches, but the haematopoietic stem cell (HSC) niche remains incompletely defined and beset by competing models. Recent progress has been made in elucidating the location and cellular components of the HSC niche in the bone marrow. The niche is perivascular, created partly by mesenchymal stromal cells and endothelial cells and often, but not always, located near trabecular bone. Outstanding questions concern the cellular complexity of the niche, the role of the endosteum and functional heterogeneity among perivascular microenvironments.
Topics: Animals; Bone Marrow; Bone and Bones; Endothelial Cells; Hematopoietic Stem Cells; Humans; Mesenchymal Stem Cells; Osteoblasts; Stem Cell Niche
PubMed: 24429631
DOI: 10.1038/nature12984 -
Current Opinion in Hematology Jan 2021The bone marrow is the main site for hematopoiesis. It contains a unique microenvironment that provides niches that support self-renewal and differentiation of... (Review)
Review
PURPOSE OF REVIEW
The bone marrow is the main site for hematopoiesis. It contains a unique microenvironment that provides niches that support self-renewal and differentiation of hematopoietic stem cells (HSC), multipotent progenitors (MPP), and lineage committed progenitors to produce the large number of blood cells required to sustain life. The bone marrow is notoriously difficult to image; because of this the anatomy of blood cell production -- and how local signals spatially organize hematopoiesis -- are not well defined. Here we review our current understanding of the spatial organization of the mouse bone marrow with a special focus in recent advances that are transforming our understanding of this tissue.
RECENT FINDINGS
Imaging studies of HSC and their interaction with candidate niches have relied on ex-vivo imaging of fixed tissue. Two recent manuscripts demonstrating live imaging of subsets of HSC in unperturbed bone marrow have revealed unexpected HSC behavior and open the door to examine HSC regulation, in situ, over time. We also discuss recent findings showing that the bone marrow contains distinct microenvironments, spatially organized, that regulate unique aspects of hematopoiesis.
SUMMARY
Defining the spatial architecture of hematopoiesis in the bone marrow is indispensable to understand how this tissue ensures stepwise, balanced, differentiation to meet organism demand; for deciphering alterations to hematopoiesis during disease; and for designing organ systems for blood cell production ex vivo.
Topics: Animals; Bone Marrow; Hematopoiesis; Hematopoietic Stem Cells; Humans; Stem Cell Niche
PubMed: 33177411
DOI: 10.1097/MOH.0000000000000621 -
Cancer Reports (Hoboken, N.J.) Apr 2019Carcinogenic transformation of white blood cells during hematopoiesis leads to the development of leukemia, a cancer characterized by incompetent immune cells and a... (Review)
Review
BACKGROUND
Carcinogenic transformation of white blood cells during hematopoiesis leads to the development of leukemia, a cancer characterized by incompetent immune cells and a disruption of normal bone marrow function. Leukemias are diverse in type, affected population, prognosis, and treatment regimen, yet a common theme in leukemia is the dysregulated metabolism of leukemic cells and leukemic stem cells with respect to their noncancerous counterparts.
RECENT FINDINGS
In this review, we highlight current findings that elucidate metabolic traits unique to the four major types of leukemia, which confer carcinogenic survival but can be potentially exploited for therapeutic intervention. These metabolic features can work in conjunction with or be independent of unique aspects of the bone marrow microenvironment that can also influence cell survival and proliferation, thus sustaining carcinogenesis.
CONCLUSION
Deepening our understanding of the interactions of leukemias with their niche environments in vivo will inform future treatments for leukemia, particularly for those that are refractive to tyrosine kinase inhibitors and other therapeutic mainstays.
Topics: Animals; Bone Marrow; Hematopoiesis; Humans; Leukemia; Metabolic Networks and Pathways; Stem Cell Niche; Tumor Microenvironment
PubMed: 32721091
DOI: 10.1002/cnr2.1139 -
Current Osteoporosis Reports Dec 2016This study aims to describe bone marrow fat changes in diabetes and to discuss the potential role of marrow fat in skeletal fragility. (Review)
Review
PURPOSE OF REVIEW
This study aims to describe bone marrow fat changes in diabetes and to discuss the potential role of marrow fat in skeletal fragility.
RECENT FINDINGS
Advances in non-invasive imaging have facilitated marrow fat research in humans. In contrast to animal studies which clearly demonstrate higher levels of marrow fat in diabetes, human studies have shown smaller and less certain differences. Marrow fat has been reported to correlate with A1c, and there may be a distinct marrow lipid saturation profile in diabetes. Greater marrow fat is associated with impaired skeletal health. Marrow fat may be a mediator of skeletal fragility in diabetes. Circulating lipids, growth hormone alterations, visceral adiposity, and hypoleptinemia have been associated with greater marrow fat and may represent potential mechanisms for the putative effects of diabetes on marrow fat, although other factors likely contribute. Additional research is needed to further define the role of marrow fat in diabetic skeletal fragility and to determine whether marrow fat is a therapeutic target.
Topics: Adipose Tissue; Adiposity; Animals; Bone Density; Bone Marrow; Diabetes Mellitus; Humans; Magnetic Resonance Imaging; Osteoblasts; Osteoporosis; Proton Magnetic Resonance Spectroscopy
PubMed: 27714580
DOI: 10.1007/s11914-016-0336-x -
Cells Apr 2024Bone marrow (BM) acts as a dynamic organ within the bone cavity, responsible for hematopoiesis, skeletal remodeling, and immune system control. Bone marrow adipose... (Review)
Review
Bone marrow (BM) acts as a dynamic organ within the bone cavity, responsible for hematopoiesis, skeletal remodeling, and immune system control. Bone marrow adipose tissue (BMAT) was long simply considered a filler of space, but now it is known that it instead constitutes an essential element of the BM microenvironment that participates in homeostasis, influences bone health and bone remodeling, alters hematopoietic stem cell functions, contributes to the commitment of mesenchymal stem cells, provides effects to immune homeostasis and defense against infections, and participates in energy metabolism and inflammation. BMAT has emerged as a significant contributor to the development and progression of various diseases, shedding light on its complex relationship with health. Notably, BMAT has been implicated in metabolic disorders, hematological malignancies, and skeletal conditions. BMAT has been shown to support the proliferation of tumor cells in acute myeloid leukemia and niche adipocytes have been found to protect cancer cells against chemotherapy, contributing to treatment resistance. Moreover, BMAT's impact on bone density and remodeling can lead to conditions like osteoporosis, where high levels of BMAT are inversely correlated with bone mineral density, increasing the risk of fractures. BMAT has also been associated with diabetes, obesity, and anorexia nervosa, with varying effects on individuals depending on their weight and health status. Understanding the interaction between adipocytes and different diseases may lead to new therapeutic strategies.
Topics: Humans; Adipose Tissue; Bone Marrow; Animals
PubMed: 38727260
DOI: 10.3390/cells13090724 -
Endocrine Reviews Oct 2019The presence of adipocytes in mammalian bone marrow (BM) has been recognized histologically for decades, yet, until recently, these cells have received little attention... (Review)
Review
The presence of adipocytes in mammalian bone marrow (BM) has been recognized histologically for decades, yet, until recently, these cells have received little attention from the research community. Advancements in mouse transgenics and imaging methods, particularly in the last 10 years, have permitted more detailed examinations of marrow adipocytes than ever before and yielded data that show these cells are critical regulators of the BM microenvironment and whole-body metabolism. Indeed, marrow adipocytes are anatomically and functionally separate from brown, beige, and classic white adipocytes. Thus, areas of BM space populated by adipocytes can be considered distinct fat depots and are collectively referred to as marrow adipose tissue (MAT) in this review. In the proceeding text, we focus on the developmental origin and physiologic functions of MAT. We also discuss the signals that cause the accumulation and loss of marrow adipocytes and the ability of these cells to regulate other cell lineages in the BM. Last, we consider roles for MAT in human physiology and disease.
Topics: Adipocytes; Adiposity; Animals; Bone Marrow; Humans; Signal Transduction
PubMed: 31127816
DOI: 10.1210/er.2018-00138 -
Trends in Endocrinology and Metabolism:... Jun 2022Recent studies have highlighted the role of bone marrow adipose tissue (BMAT) as a regulator of skeletal homeostasis and energy metabolism. While long considered an... (Review)
Review
Recent studies have highlighted the role of bone marrow adipose tissue (BMAT) as a regulator of skeletal homeostasis and energy metabolism. While long considered an inert filler, occupying empty spaces from bone loss and reduced hematopoiesis, BMAT is now considered a secretory and metabolic organ that responds to nutritional challenges and secretes cytokines, which indirectly impact energy and bone metabolism. The recent advances in our understanding of the function of BMAT have been enabled by novel noninvasive imaging techniques, which allow longitudinal assessment of BMAT in vivo following interventions. This review will focus on the latest advances in our understanding of BMAT and its role in metabolic health. Imaging techniques to quantify the content and composition of BMAT will be discussed.
Topics: Adipose Tissue; Bone Marrow; Energy Metabolism; Humans
PubMed: 35396163
DOI: 10.1016/j.tem.2022.03.003 -
Frontiers in Endocrinology 2020Obesity is characterized by low-grade inflammation, which is accompanied by increased accumulation of immune cells in peripheral tissues including adipose tissue (AT),... (Review)
Review
Obesity is characterized by low-grade inflammation, which is accompanied by increased accumulation of immune cells in peripheral tissues including adipose tissue (AT), skeletal muscle, liver and pancreas, thereby impairing their primary metabolic functions in the regulation of glucose homeostasis. Obesity has also shown to have a detrimental effect on bone homeostasis by altering bone marrow and hematopoietic stem cell differentiation and thus impairing bone integrity and immune cell properties. The origin of immune cells arises in the bone marrow, which has been shown to be affected with the obesogenic condition via increased cellularity and shifting differentiation and function of hematopoietic and bone marrow mesenchymal stem cells in favor of myeloid progenitors and increased bone marrow adiposity. These obesity-induced changes in the bone marrow microenvironment lead to dramatic bone marrow remodeling and compromising immune cell functions, which in turn affect systemic inflammatory conditions and regulation of whole-body metabolism. However, there is limited information on the inflammatory secretory factors creating the bone marrow microenvironment and how these factors changed during metabolic complications. This review summarizes recent findings on inflammatory and cellular changes in the bone marrow in relation to obesity and further discuss whether dietary intervention or physical activity may have beneficial effects on the bone marrow microenvironment and whole-body metabolism.
Topics: Animals; Bone Marrow; Cellular Microenvironment; Hematopoiesis; Hematopoietic Stem Cells; Humans; Obesity
PubMed: 32477271
DOI: 10.3389/fendo.2020.00294 -
Bone Jan 2019Bone strength is affected not only by bone mineral density (BMD) and bone microarchitecture but also its microenvironment. Recent studies have focused on the role of... (Review)
Review
Bone strength is affected not only by bone mineral density (BMD) and bone microarchitecture but also its microenvironment. Recent studies have focused on the role of marrow adipose tissue (MAT) in the pathogenesis of bone loss. Osteoblasts and adipocytes arise from a common mesenchymal stem cell within bone marrow and many osteoporotic states, including aging, medication use, immobility, over - and undernutrition are associated with increased marrow adiposity. Advancements in imaging technology allow the non-invasive quantification of MAT. This article will review magnetic resonance imaging (MRI)- and computed tomography (CT)-based imaging technologies to assess the amount and composition of MAT. The techniques that will be discussed are anatomic T1-weighted MRI, water-fat imaging, proton MR spectroscopy, single energy CT and dual energy CT. Clinical applications of MRI and CT techniques to determine the role of MAT in patients with obesity, anorexia nervosa, and type 2 diabetes will be reviewed.
Topics: Adipose Tissue; Adiposity; Bone Marrow; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Water
PubMed: 29331301
DOI: 10.1016/j.bone.2018.01.009 -
International Journal of Molecular... Feb 2021Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis... (Review)
Review
Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis and in establishing chemotherapy and hematopoietic stem cell transplantation therapy (HSCT). However, while the successive development of new therapies, such as molecular-targeted therapy and immunotherapy, have resulted in remarkable advances, the fact remains that some patients still cannot be saved, and resistance to treatment and relapse are still problems that need to be solved in leukemia patients. The bone marrow (BM) niche is a microenvironment that includes hematopoietic stem cells and their supporting cells. Leukemia cells interact with bone marrow niches and modulate them, not only inducing molecular and functional changes but also switching to niches favored by leukemia cells. The latter are closely associated with leukemia progression, suppression of normal hematopoiesis, and chemotherapy resistance, which is precisely the area of ongoing study. Exosomes play an important role in cell-to-cell communication, not only with cells in close proximity but also with those more distant due to the nature of exosomal circulation via body fluids. In leukemia, exosomes play important roles in leukemogenesis, disease progression, and organ invasion, and their usefulness in the diagnosis and treatment of leukemia has recently been reported. The interaction between leukemia cell-derived exosomes and the BM microenvironment has received particular attention. Their interaction is believed to play a very important role; in addition to their diagnostic value, exosomes could serve as a marker for monitoring treatment efficacy and as an aid in overcoming drug resistance, among the many problems in leukemia patients that have yet to be overcome. In this paper, we will review bone marrow niches in leukemia, findings on leukemia-derived exosomes, and exosome-induced changes in bone marrow niches.
Topics: Bone Marrow; Cell Communication; Exosomes; Humans; Leukemia; Tumor Microenvironment
PubMed: 33668652
DOI: 10.3390/ijms22041881