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Life Sciences Jul 2022Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important... (Review)
Review
Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important regulator of platelet production and immunoregulation. However, dysfunction in MKs is considered a trigger in various diseases. It has been described that the lung is an important site of platelet biogenesis from extramedullary MKs, which may play an essential role in various pulmonary diseases. With detailed studies, there are different degrees of numerical changes of MKs in coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis (PF), and other pulmonary diseases. Also, MKs inhibit or promote the development of pulmonary diseases through various pathways. Here, we summarize the current knowledge of MKs in pulmonary diseases, highlighting the physiological functions and integrated molecular mechanisms. We aim to shine new light on not only the subsequent study of MKs but also the diagnosis and treatment of pulmonary diseases.
Topics: Blood Platelets; COVID-19; Humans; Lung; Megakaryocytes; Respiratory Distress Syndrome; Thrombopoiesis
PubMed: 35508253
DOI: 10.1016/j.lfs.2022.120602 -
Journal of Cell Science Oct 2020The main function of blood platelets is to ensure hemostasis and prevent hemorrhages. The 10 platelets needed daily are produced in a well-orchestrated process. However,... (Review)
Review
The main function of blood platelets is to ensure hemostasis and prevent hemorrhages. The 10 platelets needed daily are produced in a well-orchestrated process. However, this process is not yet fully understood and platelet production is still inefficient. Platelets are produced in the bone marrow by megakaryocytes, highly specialized precursor cells that extend cytoplasmic projections called proplatelets (PPTs) through the endothelial barrier of sinusoid vessels. In this Cell Science at a Glance article and the accompanying poster we discuss the mechanisms and pathways involved in megakaryopoiesis and platelet formation processes. We especially address the - still underestimated - role of the microenvironment of the bone marrow, and present recent findings on how PPT extension differs from that and entails different mechanisms. Finally, we recapitulate old but recently revisited evidence that - although bone marrow does produce megakaryocytes and PPTs - remodeling and the release of bona fide platelets, mainly occur in the downstream microcirculation.
Topics: Blood Platelets; Bone Marrow; Cytoplasm; Megakaryocytes; Thrombopoiesis
PubMed: 33127839
DOI: 10.1242/jcs.244731 -
Blood Jan 2023
Topics: Humans; Glycosylation; Thrombopoiesis; Mutation; Thrombocytopenia
PubMed: 36701170
DOI: 10.1182/blood.2022019021 -
Current Opinion in Hematology Nov 2021This review highlights recent advancements in understanding the regulation of platelet numbers, focusing on mechanisms by which carbohydrates (glycans) link platelet... (Review)
Review
PURPOSE OF THE REVIEW
This review highlights recent advancements in understanding the regulation of platelet numbers, focusing on mechanisms by which carbohydrates (glycans) link platelet removal with platelet production in the bone marrow in health and disease.
RECENT FINDINGS
This review is focused on the role of carbohydrates, specifically sialic acid moieties, as a central mediator of platelet clearance. We discuss recently identified novel mechanisms of carbohydrate-mediated platelet removal and carbohydrate-binding receptors that mediate platelet removal.
SUMMARY
The platelet production rate by megakaryocytes and removal kinetics controls the circulating platelet count. Alterations in either process can lead to thrombocytopenia (low platelet count) or thrombocytosis (high platelet count) are associated with the risk of bleeding or overt thrombus formation and serious complications. Thus, regulation of a steady-state platelet count is vital in preventing adverse events. There are few mechanisms delineated that shed light on carbohydrates' role in the complex and massive platelet removal process. This review focuses on carbohydrate-related mechanisms that contribute to the control of platelet numbers.
Topics: Blood Platelets; Humans; Megakaryocytes; Platelet Count; Polysaccharides; Thrombopoiesis
PubMed: 34605444
DOI: 10.1097/MOH.0000000000000682 -
Thrombosis Research Nov 2023Autophagy, the continuous recycling of intracellular building blocks, molecules, and organelles is necessary to preserve cellular function and homeostasis. In this... (Review)
Review
Autophagy, the continuous recycling of intracellular building blocks, molecules, and organelles is necessary to preserve cellular function and homeostasis. In this context, it was demonstrated that autophagy plays an important role in megakaryopoiesis, the development and differentiation of hematopoietic progenitor cells into megakaryocytes. Furthermore, in recent years, autophagic proteins were detected in platelets, anucleate cells generated by megakaryocytes, responsible for hemostasis, thrombosis, and a key cell in inflammation and host immune responses. In the last decade studies have indicated the occurrence of autophagy in platelets. Moreover, autophagy in platelets was subsequently demonstrated to be involved in platelet aggregation, adhesion, and thrombus formation. Here, we review the current knowledge about autophagy in platelets, its function, and clinical implications. However, at the advent of platelet autophagy research, additional discoveries derived from evolving work will be required to precisely define the contributions of autophagy in platelets, and to expand the ever increasing physiologic and pathologic roles these remarkable and versatile blood cells play.
Topics: Humans; Blood Platelets; Megakaryocytes; Thrombopoiesis; Thrombosis; Autophagy; Biology
PubMed: 36058760
DOI: 10.1016/j.thromres.2022.08.019 -
Frontiers in Immunology 2022Platelets, generated from precursor megakaryocytes (MKs), are central mediators of hemostasis and thrombosis. The process of thrombopoiesis is extremely complex,... (Review)
Review
Platelets, generated from precursor megakaryocytes (MKs), are central mediators of hemostasis and thrombosis. The process of thrombopoiesis is extremely complex, regulated by multiple factors, and related to many cellular events including apoptosis. However, the role of apoptosis in thrombopoiesis has been controversial for many years. Some researchers believe that apoptosis is an ally of thrombopoiesis and platelets production is apoptosis-dependent, while others have suggested that apoptosis is dispensable for thrombopoiesis, and is even inhibited during this process. In this review, we will focus on this conflict, discuss the relationship between megakaryocytopoiesis, thrombopoiesis and apoptosis. In addition, we also consider why such a vast number of studies draw opposite conclusions of the role of apoptosis in thrombopoiesis, and try to figure out the truth behind the mystery. This review provides more comprehensive insights into the relationship between megakaryocytopoiesis, thrombopoiesis, and apoptosis and finds some clues for the possible pathological mechanisms of platelet disorders caused by abnormal apoptosis.
Topics: Megakaryocytes; Thrombopoiesis; Blood Platelets; Hemostasis; Apoptosis; Fenbendazole
PubMed: 36685543
DOI: 10.3389/fimmu.2022.1025945 -
Current Opinion in Hematology Nov 2021Platelet transfusion can be life-saving but carries a risk of infection or alloimmunization and is limited by insufficient donor sources and restricted unit shelf life.... (Review)
Review
PURPOSE OF REVIEW
Platelet transfusion can be life-saving but carries a risk of infection or alloimmunization and is limited by insufficient donor sources and restricted unit shelf life. Generating sufficient platelets in vitro to replace a unit of collected blood remains a challenge. Here, we examine the latest advances in the regulation of megakaryocyte maturation and expansion along with platelet formation and survival. We also discuss alternative therapies investigated to induce platelet production.
RECENT FINDINGS
Recent studies examined candidate niche cells in the bone marrow microenvironment for promoting platelet formation and developed an explant-based bioreactor to enhance platelet production ex vivo. Chemical inhibitors were examined for their ability to promote megakaryocyte maturation and expansion. Microparticles from megakaryocytes or platelets were found to improve megakaryocyte maturation and platelet formation. Membrane budding was identified as a novel mode of platelet formation. Lastly, a chemical inhibitor to improve cold-stored platelets was identified.
SUMMARY
Recent advances in the regulation of megakaryocyte expansion and platelet production provide exciting promise for the development of improved approaches to generate platelets in vitro. These findings bring the field one step closer to achieving the ultimate goal of creating a unit of platelets without the need for donation.
Topics: Blood Platelets; Bone Marrow; Humans; Megakaryocytes; Platelet Transfusion; Thrombopoiesis
PubMed: 34232141
DOI: 10.1097/MOH.0000000000000662 -
Platelets Dec 2023Inherited thrombocytopenia (IT) is a group of hereditary disorders characterized by a reduced platelet count as the main clinical manifestation, and often with abnormal... (Review)
Review
Inherited thrombocytopenia (IT) is a group of hereditary disorders characterized by a reduced platelet count as the main clinical manifestation, and often with abnormal platelet function, which can subsequently lead to impaired hemostasis. In the past decades, humanized mouse models (HMMs), that are mice engrafted with human cells or genes, have been widely used in different research areas including immunology, oncology, and virology. With advances of the development of immunodeficient mice, the engraftment, and reconstitution of functional human platelets in HMM permit studies of occurrence and development of platelet disorders including IT and treatment strategies. This article mainly reviews the development of humanized mice models, the construction methods, research status, and problems of using humanized mice for the study of human thrombopoiesis.
Topics: Animals; Mice; Humans; Disease Models, Animal; Blood Platelets; Thrombopoiesis; Thrombocytopenia; Blood Platelet Disorders; Hematopoietic Stem Cell Transplantation
PubMed: 37849076
DOI: 10.1080/09537104.2023.2267676 -
Annals of Hematology Jun 2020Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of... (Review)
Review
Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of time. Some studies reported cases of thrombocytopenia, but hardly any studies mentioned how the virus causes thrombocytopenia. We propose several mechanisms by which coronavirus disease 2019 causes thrombocytopenia to better understand this disease and provide more clinical treatment options.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Leukopenia; Pandemics; Pneumonia, Viral; SARS-CoV-2; Thrombocytopenia; Thrombopoiesis; COVID-19 Drug Treatment
PubMed: 32296910
DOI: 10.1007/s00277-020-04019-0