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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 -
Toxicologic Pathology 2006While a complete blood count provides information regarding possible treatment-related effects reflected in the peripheral blood, morphological evaluation of bone marrow... (Review)
Review
While a complete blood count provides information regarding possible treatment-related effects reflected in the peripheral blood, morphological evaluation of bone marrow cytology and paraffin sections provides information about bone marrow tissue architecture that otherwise would be missed by examination of peripheral blood alone. In decalcified, paraffin-embedded, hematoxylin and eosin (H&E)-stained sections of bone marrow, the more mature stages of the erythroid and myeloid cells, adipocytes, mast cells, and megakaryocytes can be identified, but lymphoid cells as well as immature progenitor cells can not be reliably identified. The quality of the marrow sections is governed by numerous variables related to specimen collection and processing and must be considered. In addition to discussing normal structure, function, and histology of bone marrow, methods for preparation and evaluation of bone marrow are presented.
Topics: Animals; Biopsy; Bone Marrow; Dogs; Hematopoiesis; Histological Techniques; Mice; Rats
PubMed: 17067943
DOI: 10.1080/01926230600939856 -
Nature Reviews. Rheumatology Aug 2023Spondyloarthritis (SpA) is characterized by the infiltration of innate and adaptive immune cells into entheses and bone marrow. Molecular, cellular and imaging evidence... (Review)
Review
Spondyloarthritis (SpA) is characterized by the infiltration of innate and adaptive immune cells into entheses and bone marrow. Molecular, cellular and imaging evidence demonstrates the presence of bone marrow inflammation, a hallmark of SpA. In the spine and the peripheral joints, bone marrow is critically involved in the pathogenesis of SpA. Evidence suggests that bone marrow inflammation is associated with enthesitis and that there are roles for mechano-inflammation and intestinal inflammation in bone marrow involvement in SpA. Specific cell types (including mesenchymal stem cells, innate lymphoid cells and γδ T cells) and mediators (Toll-like receptors and cytokines such as TNF, IL-17A, IL-22, IL-23, GM-CSF and TGFβ) are involved in these processes. Using this evidence to demonstrate a bone marrow rather than an entheseal origin for SpA could change our understanding of the disease pathogenesis and the relevant therapeutic approach.
Topics: Humans; Immunity, Innate; Bone Marrow; Lymphocytes; Spondylarthritis; Inflammation; Axial Spondyloarthritis
PubMed: 37407716
DOI: 10.1038/s41584-023-00986-6 -
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 -
Current Osteoporosis Reports Dec 2019The significance and roles of marrow adipose tissue (MAT) are increasingly known, and it is no more considered a passive fat storage but a tissue with significant... (Review)
Review
PURPOSE OF REVIEW
The significance and roles of marrow adipose tissue (MAT) are increasingly known, and it is no more considered a passive fat storage but a tissue with significant paracrine and endocrine activities that can cause lipotoxicity and inflammation.
RECENT FINDINGS
Changes in the MAT volume and fatty acid composition appear to drive bone and hematopoietic marrow deterioration, and studying it may open new horizons to predict bone fragility and anemia development. MAT has the potential to negatively impact bone volume and strength through several mechanisms that are partially described by inflammaging and lipotoxicity terminology. Evidence indicates paramount importance of MAT in age-associated decline of bone and red marrow structure and function. Currently, MAT measurement is being tested and validated by several techniques. However, purpose-specific adaptation of existing imaging technologies and, more importantly, development of new modalities to quantitatively measure MAT are yet to be done.
Topics: Adipose Tissue; Animals; Bone Marrow; Bone and Bones; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Organ Size; Tomography, X-Ray Computed
PubMed: 31713178
DOI: 10.1007/s11914-019-00539-5 -
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 -
Journal of Intensive Care Medicine 1995Bone marrow necrosis is regarded as an uncommon entity that is associated with a poor prognosis. However, organized studies using either bone marrow biopsy specimens or... (Review)
Review
Bone marrow necrosis is regarded as an uncommon entity that is associated with a poor prognosis. However, organized studies using either bone marrow biopsy specimens or autopsy material showed that bone marrow necrosis can be demonstrated in approximately one third of specimens. It is found in a large number of both malignant and nonmalignant disorders, in addition to occurring following large exposures to radiation or high dose cancer chemotherapy. In the absence of radiation or cancer chemotherapy, it probably eventuates from either vascular occlusion or blood stasis in small blood vessels. When bone marrow necrosis is prolonged, it may be associated with the development of bone marrow fibrosis, and it may serve as a predisposing etiology for idiopathic myelofibrosis. Most patients discovered with bone marrow necrosis have few symptoms, and they are eventually lost to follow-up without evident progression or development of a clinical illness. In acute disorders and in those who undergo effective therapy, recovery appears to occur without complications. This frequently overlooked finding is the subject of many case reports in the medical literature, but it has only been rarely systematically investigated. The latter is probably warranted because of the potential role of bone marrow necrosis in the pathophysiology of a number of disorders and the paucity of information for treatment of this pathological finding.
Topics: Bone Marrow; Bone Marrow Diseases; Humans; Microcirculation; Necrosis; Primary Myelofibrosis; Prognosis
PubMed: 10155181
DOI: 10.1177/088506669501000403 -
Nature Reviews. Endocrinology Nov 2023Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis,... (Review)
Review
Adipose tissue is a dynamic component of the bone marrow, regulating skeletal remodelling and secreting paracrine and endocrine factors that can affect haematopoiesis, as well as potentially nourishing the bone marrow during periods of stress. Bone marrow adipose tissue is regulated by multiple factors, but particularly nutrient status. In this Review, we examine how bone marrow adipocytes originate, their function in normal and pathological states and how bone marrow adipose tissue modulates whole-body homoeostasis through actions on bone cells, haematopoietic stem cells and extra-medullary adipocytes during nutritional challenges. We focus on both rodent models and human studies to help understand the unique marrow adipocyte, its response to the external nutrient environment and its effects on the skeleton. We finish by addressing some critical questions that to date remain unanswered.
Topics: Humans; Adipocytes; Adipose Tissue; Bone Marrow; Bone Marrow Cells; Obesity; Weight Loss
PubMed: 37587198
DOI: 10.1038/s41574-023-00879-4 -
La Radiologia Medica Feb 2021Magnetic resonance imaging (MRI) plays a leading role in the non-invasive evaluation of bone marrow (BM). Normal BM pattern depends on the ratio and distribution of... (Review)
Review
Magnetic resonance imaging (MRI) plays a leading role in the non-invasive evaluation of bone marrow (BM). Normal BM pattern depends on the ratio and distribution of yellow and red marrow, which are subject to changes with age, pathologies, and treatments. Neonates show almost entirely red marrow. Over time, yellow marrow conversion takes place with a characteristic sequence leading to a red marrow persistence in proximal metaphyses of long bones. In adults, normal BM is composed of both red (40% water, 40% fat) and yellow marrow (15% water, 80% fat). Due to the higher content of fat, yellow marrow normally appears hyperintense on T1-weighted (T1w) fast spin echo (FSE) sequences and hypo-/iso-intense in short tau inversion recovery (STIR) T2-weighted (T2w); red marrow appears slightly hyperintense in T1w FSE and hyper-/iso-intense in STIR T2w. Pathologic BM has reduced fat and increased water percentages, resulting hypointense in T1w FSE and hyperintense in STIR T2w. In oncologic patients, BM MRI signal largely depends on the treatment (irradiation and/or chemotherapy) and its timing. BM fat and water amount and location in normal red/yellow and pathologic marrow are responsible for different signals in MRI sequences whose knowledge by radiologists may help to differentiate between normal and pathologic findings. Our aim was to discuss and illustrate the MRI of BM physiologic conversion and pathologic reconversion occurring in malignancies and after treatments in cancer patients.
Topics: Bone Marrow; Bone Marrow Diseases; Humans; Magnetic Resonance Imaging
PubMed: 32557107
DOI: 10.1007/s11547-020-01239-2 -
Journal of Clinical and Experimental... 2018