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American Journal of Physical Medicine &... Dec 2018Individuals with cerebral palsy exhibit neuromuscular complications and low physical activity levels. Adults with cerebral palsy exhibit a high prevalence of chronic... (Review)
Review
Individuals with cerebral palsy exhibit neuromuscular complications and low physical activity levels. Adults with cerebral palsy exhibit a high prevalence of chronic diseases, which is associated with musculoskeletal deficits. Children with cerebral palsy have poor musculoskeletal accretion accompanied by excess bone marrow fat, which may lead to weaker bones. Mechanistic studies to determine the role of bone marrow fat on skeletal growth and maintenance and how it relates to systemic energy metabolism among individuals with cerebral palsy are lacking. In this review, we highlight the skeletal status in children with cerebral palsy and analyze the existing literature on the interactions among bone marrow fat, skeletal health, and cardiometabolic disease risk in the general population. Clinically vital questions are proposed, including the following: (1) Is the bone marrow fat in children with cerebral palsy metabolically distinct from typically developing children in terms of its lipid and inflammatory composition? (2) Does the bone marrow fat suppress skeletal acquisition? (3) Or, does it accelerate chronic disease development in children with cerebral palsy? (4) If so, what are the mechanisms? In conclusion, although inadequate mechanical loading may initiate poor skeletal development, subsequent expansion of bone marrow fat may further impede skeletal acquisition and increase cardiometabolic disease risk in those with cerebral palsy.
Topics: Adipose Tissue; Bone Density; Bone Diseases, Developmental; Bone Marrow; Cardiovascular Diseases; Cerebral Palsy; Child; Cytokines; Fractures, Bone; Glucose Metabolism Disorders; Humans; Inflammation; Lipid Metabolism
PubMed: 29894311
DOI: 10.1097/PHM.0000000000000981 -
Biology of Blood and Marrow... Oct 2018Hematopoietic cell transplantation (HCT) is increasingly utilized as a treatment for malignancies in the elderly population. At the same time, research has elucidated... (Review)
Review
Hematopoietic cell transplantation (HCT) is increasingly utilized as a treatment for malignancies in the elderly population. At the same time, research has elucidated the impacts of HCT on bone marrow progenitor cells, one of which is accelerated aging. Clonal hematopoiesis has also been observed to occur in the aging population, both with and without HCT. The interplay between natural aging, clonal hemoatpoiesis, and the effects of HCT on the bone marrow, has not yet been addressed. Herein we explore this relationship, and its important clinical implications.
Topics: Aged; Aged, 80 and over; Aging; Bone Marrow; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Neoplasms
PubMed: 30130587
DOI: 10.1016/j.bbmt.2018.08.015 -
Journal of Bone and Mineral Research :... Apr 2017Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with... (Meta-Analysis)
Meta-Analysis Review
Blood cell production and bone homeostasis are physically interlinked systems that exhibit active cross-talk. We examined how bone health is affected in patients with hematopoietic disorders due to abnormal proliferation of bone marrow cells. The electronic databases Medline, Embase, PubMed, BIOSIS Previews, Web of Science, and Cochrane were searched for studies presenting numerical values for trabecular bone volume or bone mineral density in control and patients with hematopoietic disorders. We identified 5 studies for beta-thalassemia, 6 for sickle cell anemia, 2 for polycythemia vera and essential thrombocythemia, 3 for chronic myelogenous leukemia, 6 for myelofibrosis, 5 for multiple myeloma, and 4 studies each for systemic mastocytosis, lymphocytic leukemia, and hemochromatosis. The effect of the disease state on bone density was significant and negative for beta-thalassemia (r = -2.00; 95% confidence interval [CI] -3.41, -0.58; p < 0.005), sickle cell anemia (-0.91; -1.36, -0.47; p < 0.00005), chronic myelogenous leukemia (-0.55; -0.88, -0.22; p < 0005), mastocytosis (-0.99; -1.16, -0.82; p < 0.00001), lymphoblastic leukemia (-0.69; -0.98, -0.40; p < 0.00001), multiple myeloma (-0.67; -0.99, -0.35; p < 0.00005), and hemochromatosis (-1.15; -1.64, -0.66; p < 0.00001). The changes were negative but not significant for polycythemia vera (-0.16; -0.38, 0.05; p = 0.069) and essential thrombocythemia (-0.33; -0.92, 0.26; p = 0.14). In myelofibrosis, disease state was associated with increased bone density (0.74; 0.12, 1.36; p < 0.05). Bone density change significantly and negatively correlated with the level of ferritin and bone marrow cellularity but not with hemoglobin or erythropoietin. Thus, independent of hematopoietic lineage, abnormal proliferation of bone marrow cells appears to be associated with bone loss. Iron metabolism may independently contribute to bone homeostasis. © 2016 American Society for Bone and Mineral Research.
Topics: Bone Density; Bone Marrow; Bone Marrow Cells; Bone Marrow Diseases; Cell Proliferation; Female; Ferritins; Homeostasis; Humans; Male
PubMed: 27787922
DOI: 10.1002/jbmr.3026 -
Frontiers in Cellular and Infection... 2023Leishmaniasis is a widespread group of infectious diseases that significantly impact global health. Despite high prevalence, leishmaniasis often receives inadequate... (Review)
Review
Leishmaniasis is a widespread group of infectious diseases that significantly impact global health. Despite high prevalence, leishmaniasis often receives inadequate attention in the prioritization of measures targeting tropical diseases. The causative agents of leishmaniasis are protozoan parasites of the genus, which give rise to a diverse range of clinical manifestations, including cutaneous and visceral forms. Visceral leishmaniasis (VL), the most severe form, can be life-threatening if left untreated. Parasites can spread systemically within the body, infecting a range of organs, such as the liver, spleen, bone marrow and lymph nodes. Natural reservoirs for these protozoa include rodents, dogs, foxes, jackals, and wolves, with dogs serving as the primary urban reservoir for . Dogs exhibit clinical and pathological similarities to human VL and are valuable models for studying disease progression. Both human and canine VL provoke clinical symptoms, such as organ enlargement, fever, weight loss and abnormal gamma globulin levels. Hematologic abnormalities have also been observed, including anemia, leukopenia with lymphocytosis, neutropenia, and thrombocytopenia. Studies in dogs have linked these hematologic changes in peripheral blood to alterations in the bone marrow. Mouse models of VL have also contributed significantly to our understanding of the mechanisms underlying these hematologic and bone marrow abnormalities. This review consolidates information on hematological and immunological changes in the bone marrow of humans, dogs, and mice infected with species causing VL. It includes findings on the role of bone marrow as a source of parasite persistence in internal organs and VL development. Highlighting gaps in current knowledge, the review emphasizes the need for future research to enhance our understanding of VL and identify potential targets for novel diagnostic and therapeutic approaches.
Topics: Animals; Dogs; Humans; Mice; Leishmaniasis, Visceral; Bone Marrow; Leishmaniasis; Leishmania infantum; Skin; Dog Diseases
PubMed: 37860064
DOI: 10.3389/fcimb.2023.1261074 -
Journal of Clinical and Experimental... 2018
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Canadian Journal of Rural Medicine :... 2023
Topics: Humans; Bone Marrow; Biopsy
PubMed: 37005992
DOI: 10.4103/cjrm.cjrm_64_22 -
JCI Insight Jun 2021BACKGROUNDAdipocytes were long considered inert components of the bone marrow niche, but mouse and human models suggest bone marrow adipose tissue (BMAT) is dynamic and...
BACKGROUNDAdipocytes were long considered inert components of the bone marrow niche, but mouse and human models suggest bone marrow adipose tissue (BMAT) is dynamic and responsive to hormonal and nutrient cues.METHODSIn this study of healthy volunteers, we investigated how BMAT responds to acute nutrient changes, including analyses of endocrine determinants and paracrine factors from marrow aspirates. Study participants underwent a 10-day high-calorie protocol, followed by a 10-day fast.RESULTSWe demonstrate (a) vertebral BMAT increased significantly during high-calorie feeding and fasting, suggesting BMAT may have different functions in states of caloric excess compared with caloric deprivation; (b) ghrelin, which decreased in response to high-calorie feeding and fasting, was inversely associated with changes in BMAT; and (c) in response to high-calorie feeding, resistin levels in the marrow sera, but not the circulation, rose significantly. In addition, TNF-α expression in marrow adipocytes increased with high-calorie feeding and decreased upon fasting.CONCLUSIONHigh-calorie feeding, but not fasting, induces an immune response in bone marrow similar to what has been reported in peripheral adipose tissue. Understanding the immunomodulatory regulators in the marrow may provide further insight into the homeostatic function of this unique adipose tissue depot.FUNDINGNIH grant R24 DK084970, Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH, award UL 1TR002541), and NIH grants P30 DK040561 and U19 AG060917S1.
Topics: Adipose Tissue; Adult; Bone Marrow; Fasting; Female; Humans; Male
PubMed: 33974568
DOI: 10.1172/jci.insight.138636 -
Blood Reviews Jan 2014Use of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood hematopoietic progenitor cells (HPCs) has largely replaced bone marrow (BM) as a source... (Review)
Review
Use of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood hematopoietic progenitor cells (HPCs) has largely replaced bone marrow (BM) as a source of stem cells for both autologous and allogeneic cell transplantation. With G-CSF alone, up to 35% of patients are unable to mobilize sufficient numbers of CD34 cells/kg to ensure successful and consistent multi-lineage engraftment and sustained hematopoietic recovery. To this end, research is ongoing to identify new agents or combinations which will lead to the most effective and efficient stem cell mobilization strategies, especially in those patients who are at risk for mobilization failure. We describe both established agents and novel strategies at various stages of development. The latter include but are not limited to drugs that target the SDF-1/CXCR4 axis, S1P agonists, VCAM/VLA-4 inhibitors, parathyroid hormone, proteosome inhibitors, Groβ, and agents that stabilize HIF. While none of the novel agents have yet gained an established role in HPC mobilization in clinical practice, many early studies exploring these new pathways show promising results and warrant further investigation.
Topics: Animals; Bone Marrow; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans
PubMed: 24476957
DOI: 10.1016/j.blre.2014.01.001 -
Nature Communications Jan 2022The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca]), but the local [Ca]...
The fate of hematopoietic stem cells (HSCs) can be directed by microenvironmental factors including extracellular calcium ion concentration ([Ca]), but the local [Ca] around individual HSCs in vivo remains unknown. Here we develop intravital ratiometric analyses to quantify the absolute pH and [Ca] in the mouse calvarial bone marrow, taking into account the pH sensitivity of the calcium probe and the wavelength-dependent optical loss through bone. Unexpectedly, the mean [Ca] in the bone marrow (1.0 ± 0.54 mM) is not significantly different from the blood serum, but the HSCs are found in locations with elevated local [Ca] (1.5 ± 0.57 mM). With aging, a significant increase in [Ca] is found in M-type cavities that exclusively support clonal expansion of activated HSCs. This work thus establishes a tool to investigate [Ca] and pH in the HSC niche with high spatial resolution and can be broadly applied to other tissue types.
Topics: Aging; Animals; Benzopyrans; Bone Marrow; Bone Remodeling; Calcium; Cellular Microenvironment; Fluorescence; Hematopoietic Stem Cells; Hydrogen-Ion Concentration; Intravital Microscopy; Mice, Inbred C57BL; Naphthols; Rhodamines; Mice
PubMed: 35046411
DOI: 10.1038/s41467-022-27973-x -
Impact and Intricacies of Bone Marrow Microenvironment in B-cell Lymphomas: From Biology to Therapy.International Journal of Molecular... Jan 2020Lymphoma, a group of widely prevalent hematological malignancies of lymphocyte origin, has become the focus of significant clinical research due to their high propensity... (Review)
Review
Lymphoma, a group of widely prevalent hematological malignancies of lymphocyte origin, has become the focus of significant clinical research due to their high propensity for refractory/relapsed (R/R) disease, leading to poor prognostic outcomes. The complex molecular circuitry in lymphomas, especially in the aggressive phenotypes, has made it difficult to find a therapeutic option that can salvage R/R disease. Furthermore, the association of lymphomas with the Bone Marrow (BM) microenvironment has been found to portend worse outcomes in terms of heightened chances of relapse and acquired resistance to chemotherapy. This review assesses the current therapy options in three distinct types of lymphomas: diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma. It also explores the role of the BM tumor microenvironment as a secure 'niche' for lymphoma cells to grow, proliferate and survive. It further evaluates potential mechanisms through which the tumor cells can establish molecular connections with the BM cells to provide pro-tumor benefits, and discusses putative therapeutic strategies for disrupting the BM-lymphoma cell communication.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Drug Resistance, Neoplasm; Humans; Lymphoma, B-Cell; Tumor Microenvironment
PubMed: 32019190
DOI: 10.3390/ijms21030904