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Article ; Online: Niche heterogeneity in the bone marrow.

Birbrair, Alexander / Frenette, Paul S

Annals of the New York Academy of Sciences

2016 Volume 1370, Issue 1, Page(s) 82–96

Abstract: ... in the bone marrow (BM) microenvironment. The specific microenvironment regulating HSCs, commonly referred ... recent advances in our understanding of niche heterogeneity and its influence on HSC function. ... to as the niche, comprises multiple cell types whose exact contributions are under active investigation ...

Abstract	In adult mammals, hematopoietic stem cells (HSCs) are defined by their abilities to self-renew and to differentiate to form all blood cell lineages. These rare multipotent cells occupy specific locations in the bone marrow (BM) microenvironment. The specific microenvironment regulating HSCs, commonly referred to as the niche, comprises multiple cell types whose exact contributions are under active investigation. Understanding cellular cross talk involving HSCs in the BM microenvironment is of fundamental importance for harnessing therapies against benign and malignant blood diseases. In this review, we summarize and evaluate recent advances in our understanding of niche heterogeneity and its influence on HSC function.
MeSH term(s)	Animals ; Bone Marrow/physiology ; Bone Marrow Cells/cytology ; Bone Marrow Cells/metabolism ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Humans ; Stem Cell Niche/physiology
Language	English
Publishing date	2016-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1111/nyas.13016
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Article ; Online: Heterogeneity of the bone marrow niche.

Yu, Vionnie W C / Scadden, David T

Current opinion in hematology

2016 Volume 23, Issue 4, Page(s) 331–338

Abstract: Purpose of review: The bone marrow niche is increasingly recognized as heterogeneous with specific ... by unique cell pairings within the bone marrow and provides an overview of how the bone marrow orchestrates ... and response to acute stress signals.: Summary: The emerging concept is that the bone marrow ...

Abstract	Purpose of review: The bone marrow niche is increasingly recognized as heterogeneous with specific subtypes of mesenchymal niche cells governing the development or homeostasis of selective parenchymal hematopoietic subsets. The present review outlines recent efforts in dissecting these microniches regulated by unique cell pairings within the bone marrow and provides an overview of how the bone marrow orchestrates multiple facets of hematopoiesis. Recent findings: Recent advancement in technologies has significantly improved our understanding of the cellular and molecular constituents that contribute to regulation of hematopoiesis and to maintenance of the hematopoietic stem cells (HSCs). Transgenic mouse models that enable endogenous cell deletion or lineage tracing, coupled with advanced intravital microscopy has identified several mesenchymal cell types, including the osteolineage cells, megakaryocytes, macrophages, perivascular cells, and Schwann cells, to be indispensible regulators of hematopoiesis. These niche cells, when perturbed, each caused very specific hematopoietic consequences including impairment in B-cell maturation, T lineage development, erythropoiesis, and impact different aspects of HSC behavior such as quiescence, mobilization, and response to acute stress signals. Summary: The emerging concept is that the bone marrow environment is composed of multiple microniches, each consisting of unique pairing of distinct supportive stromal cells with distinct hematopoietic subtypes to regulate a particular branch of hematopoietic cell process. The bone marrow can be viewed as a carrier with subcompartments tailored to support different hematopoietic activities.
MeSH term(s)	Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/metabolism ; Cell Communication ; Cell Cycle ; Cell Differentiation ; Cell Movement ; Erythropoiesis ; Hematopoiesis ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Humans ; Lymphoid Progenitor Cells/cytology ; Lymphoid Progenitor Cells/metabolism ; Lymphopoiesis ; Macrophages/metabolism ; Megakaryocytes/metabolism ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Osteogenesis ; Stem Cell Niche ; Stress, Physiological ; Sympathetic Nervous System/physiology
Language	English
Publishing date	2016-03-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0000000000000265
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Article ; Online: Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis.

Rambaldi, Benedetta / Diral, Elisa / Donsante, Samantha / Di Marzo, Noemi / Mottadelli, Federica / Cardinale, Lucia / Dander, Erica / Isimbaldi, Giuseppe / Pioltelli, Pietro / Biondi, Andrea / Riminucci, Mara / D'Amico, Giovanna / Elli, Elena Maria / Pievani, Alice / Serafini, Marta

Annals of hematology

2020 Volume 100, Issue 1, Page(s) 105–116

Abstract: Mesenchymal stromal cells (MSCs) represent an essential component of the bone marrow (BM) niche and ...

Abstract	Mesenchymal stromal cells (MSCs) represent an essential component of the bone marrow (BM) niche and display disease-specific alterations in several myeloid malignancies. The aim of this work was to study possible MSC abnormalities in Philadelphia-negative myeloproliferative neoplasms (MPNs) in relationship to the degree of BM fibrosis. MSCs were isolated from BM of 6 healthy donors (HD) and of 23 MPN patients, classified in 3 groups according to the diagnosis and the grade of BM fibrosis: polycythemia vera and essential thrombocythemia (PV/ET), low fibrosis myelofibrosis (LF-MF), and high fibrosis MF (HF-MF). MSC cultures were established from 21 of 23 MPN patients. MPN-derived MSCs did not exhibit any functional impairment in their adipogenic/osteogenic/chondrogenic differentiation potential and displayed a phenotype similar to HD-derived MSCs but with a decreased expression of CD146. All MPN-MSC lines were negative for the patient-specific hematopoietic clone mutations (JAK2, MPL, CALR). MSCs derived from HF-MF patients displayed a reduced clonogenic potential and a lower growth kinetic compared to MSCs from HD, LF-MF, and PV/ET patients. mRNA levels of hematopoiesis regulatory molecules were unaffected in MSCs from HF-MF compared to HD. Finally, in vitro ActivinA secretion by MSCs was increased in HF-MF compared to LF-MF patients, in association with a lower hemoglobin value. Increased ActivinA immunolabeling on stromal cells and erythroid precursors was also observed in HF-MF BM biopsies. In conclusion, higher grade of BM fibrosis is associated with functional impairment of MSCs and the increased secretion of ActivinA may represent a suitable target for anemia treatment in MF patients.
MeSH term(s)	Activins/metabolism ; Adult ; Aged ; Bone Marrow/metabolism ; Bone Marrow/pathology ; Cell Differentiation/physiology ; Cells, Cultured ; Cohort Studies ; Female ; Humans ; Male ; Mesenchymal Stem Cells/metabolism ; Mesenchymal Stem Cells/pathology ; Middle Aged ; Myeloproliferative Disorders/metabolism ; Myeloproliferative Disorders/pathology ; Polycythemia Vera/metabolism ; Polycythemia Vera/pathology ; Primary Myelofibrosis/metabolism ; Primary Myelofibrosis/pathology ; Thrombocythemia, Essential/metabolism ; Thrombocythemia, Essential/pathology
Chemical Substances	activin A ; Activins (104625-48-1)
Language	English
Publishing date	2020-10-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1064950-5
ISSN	1432-0584 ; 0939-5555 ; 0945-8077
ISSN (online)	1432-0584
ISSN	0939-5555 ; 0945-8077
DOI	10.1007/s00277-020-04306-w
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Article ; Online: In Vivo Labeling by CD73 Marks Multipotent Stromal Cells and Highlights Endothelial Heterogeneity in the Bone Marrow Niche.

Breitbach, Martin / Kimura, Kenichi / Luis, Tiago C / Fuegemann, Christopher J / Woll, Petter S / Hesse, Michael / Facchini, Raffaella / Rieck, Sarah / Jobin, Katarzyna / Reinhardt, Julia / Ohneda, Osamu / Wenzel, Daniela / Geisen, Caroline / Kurts, Christian / Kastenmüller, Wolfgang / Hölzel, Michael / Jacobsen, Sten E W / Fleischmann, Bernd K

Cell stem cell

2018 Volume 22, Issue 2, Page(s) 262–276.e7

Abstract: Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found ... ...

Abstract	Despite much work studying ex vivo multipotent stromal cells (MSCs), the identity and characteristics of MSCs in vivo are not well defined. Here, we generated a CD73-EGFP reporter mouse to address these questions and found EGFP
MeSH term(s)	5'-Nucleotidase/metabolism ; Animals ; Bone Marrow/metabolism ; Bone Marrow Cells/cytology ; Bone Marrow Cells/metabolism ; Chondrogenesis ; Endothelial Cells/cytology ; Endothelial Cells/metabolism ; Female ; Genes, Reporter ; Green Fluorescent Proteins/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Multipotent Stem Cells/cytology ; Multipotent Stem Cells/metabolism ; Organ Specificity ; Staining and Labeling ; Stem Cell Niche ; Stromal Cells/cytology ; Stromal Cells/metabolism
Chemical Substances	enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9) ; 5'-Nucleotidase (EC 3.1.3.5)
Language	English
Publishing date	2018-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2018.01.008
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Article ; Online: Functional heterogeneity of the bone marrow vascular niche.

Kopp, Hans-Georg / Hooper, Andrea T / Avecilla, Scott T / Rafii, Shahin

Annals of the New York Academy of Sciences

2009 Volume 1176, Page(s) 47–54

Abstract: ... survival, and differentiation. Therefore, SECs are referred to as a bone marrow vascular niche (BMVN ... we show that the bone marrow vasculature comprises heterogeneous compartments. SECs are distinguished ... are still not sufficient means to identify and isolate SECs, therefore the "niche endothelial cell ...

Abstract	Sinusoidal endothelial cells (SECs) comprise the platform where trafficking into and out of the BM occurs and where hematopoietic stem and progenitor cells (HSPC) harbor and receive cues for self-renewal, survival, and differentiation. Therefore, SECs are referred to as a bone marrow vascular niche (BMVN). Hematopoietic regeneration has been shown to occur only with concurrent angiogenic regeneration. However, there are still not sufficient means to identify and isolate SECs, therefore the "niche endothelial cell" remains incompletely characterized. VEGF-receptor-3 (VEGFR3) is expressed exclusively by the SECs, while Sca1 and Tie2 are only expressed on the VEGFR3(-) arteriolar endothelium. We previously demonstrated the importance of vascular recovery in hematopoietic regeneration from myelosuppression due to cytotoxic agents or whole-body irradiation. Therefore to establish the functional importance of SECs, the mechanisms underlying BMVN regeneration were examined utilizing a 5-fluorouracil (5-FU) myelosuppression model of vascular damage. Injection of antibodies against murine VEGFR-1 and -2 had no significant effect on hemangiogenic recovery. However, when soluble VEGFR-1, a decoy receptor for VEGF-A and PlGF, was injected after 5-FU, both angiogenic remodeling and regeneration of megakaryopoiesis were delayed. In conclusion, we show that the bone marrow vasculature comprises heterogeneous compartments. SECs are distinguished from arterioles by unique immunophenotypes. Regeneration of damaged SECs is the rate-limiting step in hematopoietic regeneration from myelosuppressive therapy. Novel, high-efficiency VEGF-binding drugs in combination with chemotherapeutic agents may lead to cases of prolonged cytopenia.
MeSH term(s)	Animals ; Bone Marrow/drug effects ; Bone Marrow/physiology ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiology ; Fluorouracil/pharmacology ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/physiology ; Mice ; Mice, Inbred C57BL ; Regeneration ; Stem Cell Niche/cytology ; Stem Cell Niche/metabolism ; Stem Cell Niche/physiology ; Vascular Endothelial Growth Factor Receptor-1/antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-1/biosynthesis ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-2/biosynthesis ; Vascular Endothelial Growth Factor Receptor-3/antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-3/biosynthesis
Chemical Substances	Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-3 (EC 2.7.10.1) ; Fluorouracil (U3P01618RT)
Language	English
Publishing date	2009-09-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1111/j.1749-6632.2009.04964.x
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Article: Connecting the Dots: Resolving the Bone Marrow Niche Heterogeneity.

Dolgalev, Igor / Tikhonova, Anastasia N

Frontiers in cell and developmental biology

2021 Volume 9, Page(s) 622519

Abstract: ... including hematopoiesis and its niche within the bone marrow. Recent reports examined the bone marrow ... aging. These rapid advancements significantly informed our understanding of bone marrow niche ... interpretation of this body of work. Here, we review recent reports interrogating bone marrow niche architecture ...

Abstract	Single-cell sequencing approaches have transformed our understanding of stem cell systems, including hematopoiesis and its niche within the bone marrow. Recent reports examined the bone marrow microenvironment at single-cell resolution at steady state, following chemotherapy treatment, leukemic onset, and aging. These rapid advancements significantly informed our understanding of bone marrow niche heterogeneity. However, inconsistent representation and nomenclature among the studies hinder a comprehensive interpretation of this body of work. Here, we review recent reports interrogating bone marrow niche architecture and present an integrated overview of the published datasets.
Language	English
Publishing date	2021-03-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.622519
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Article ; Online: Bone marrow adiposity and the hematopoietic niche: A historical perspective of reciprocity, heterogeneity, and lineage commitment.

Tratwal, Josefine / Rojas-Sutterlin, Shanti / Bataclan, Charles / Blum, Sabine / Naveiras, Olaia

Best practice & research. Clinical endocrinology & metabolism

2021 Volume 35, Issue 4, Page(s) 101564

Abstract: ... Constitutive bone marrow adipose tissue (cBMAT) historically associates to the "yellow" marrow containing ... Purpose: Here we review the current knowledge on bone marrow adipocytes (BMAds) as active ... of the adipocyte lineage within the bone marrow, and how potentially different contexts dictate their interactions ...

Abstract	Purpose: Here we review the current knowledge on bone marrow adipocytes (BMAds) as active contributors to the regulation of the hematopoietic niche, and as potentially pivotal players in the progression of hematological malignancies. We highlight the hierarchical and functional heterogeneity of the adipocyte lineage within the bone marrow, and how potentially different contexts dictate their interactions with hematopoietic populations. Recent findings: Growing evidence associates the adipocyte lineage with important functions in hematopoietic regulation within the BM niche. Initially proposed to serve as negative regulators of the hematopoietic microenvironment, studies have also demonstrated that BMAds positively influence the survival and maintenance of hematopoietic stem cells (HSCs). These seemingly incongruous findings may at least be partially explained by stage-specificity across the adipocytic differentiation axis and by BMAds subtypes, suggesting that the heterogeneity of these populations allows for differential context-based interactions. One such distinction relies on the location of adipocytes. Constitutive bone marrow adipose tissue (cBMAT) historically associates to the "yellow" marrow containing so-called "stable" BMAs larger in size, less responsive to stimuli, and linked to HSC quiescence. On the other hand, regulated bone marrow adipose tissue (rBMAT)-associated adipocytes, also referred to as "labile" are smaller, more responsive to hematopoietic demand and strategically situated in hematopoietically active regions of the skeleton. Here we propose a model where the effect of distinct BM stromal cell populations (BMSC) in hematopoiesis is structured along the BMSC-BMAd differentiation axis, and where the effects on HSC maintenance versus hematopoietic proliferation are segregated. In doing so, it is possible to explain how recently identified, adipocyte-primed leptin receptor-expressing, CXCL12-high adventitial reticular cells (AdipoCARs) and marrow adipose lineage precursor cells (MALPs) best support active hematopoietic cell proliferation, while adipose progenitor cells (APCs) and maturing BMAd gradually lose the capacity to support active hematopoiesis, favoring HSC quiescence. Implicated soluble mediators include MCP-1, PAI-1, NRP1, possibly DPP4 and limiting availability of CXCL12 and SCF. How remodeling occurs within the BMSC-BMAd differentiation axis is yet to be elucidated and will likely unravel a three-way regulation of the hematopoietic, bone, and adipocytic compartments orchestrated by vascular elements. The interaction of malignant hematopoietic cells with BMAds is precisely contributing to unravel specific mechanisms of remodeling. Summary: BMAds are important operative components of the hematopoietic microenvironment. Their heterogeneity directs their ability to exert a range of regulatory capacities in a manner dependent on their hierarchical, spatial, and biological context. This complexity highlights the importance of (i) developing experimental tools and nomenclature adapted to address stage-specificity and heterogeneity across the BMSC-BMAd differentiation axis when reporting effects in hematopoiesis, (ii) interpreting gene reporter studies within this framework, and (iii) quantifying changes in all three compartments (hematopoiesis, adiposity and bone) when addressing interdependency.
MeSH term(s)	Adiposity ; Bone Marrow ; Bone Marrow Cells ; Hematopoiesis ; Humans ; Stem Cell Niche
Language	English
Publishing date	2021-08-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2052339-7
ISSN	1878-1594 ; 1532-1908 ; 1521-690X
ISSN (online)	1878-1594 ; 1532-1908
ISSN	1521-690X
DOI	10.1016/j.beem.2021.101564
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Article ; Online: Single-cell transcriptomes of murine bone marrow stromal cells reveal niche-associated heterogeneity.

Addo, Richard K / Heinrich, Frederik / Heinz, Gitta Anne / Schulz, Daniel / Sercan-Alp, Özen / Lehmann, Katrin / Tran, Cam Loan / Bardua, Markus / Matz, Mareen / Löhning, Max / Hauser, Anja E / Kruglov, Andrey / Chang, Hyun-Dong / Durek, Pawel / Radbruch, Andreas / Mashreghi, Mir-Farzin

European journal of immunology

2019 Volume 49, Issue 9, Page(s) 1372–1379

Abstract: Bone marrow (BM) stromal cells are important in the development and maintenance ... heterogeneity of individual transcriptomes of 1167 murine BM mesenchymal stromal cells. These cells exhibit ... a tremendous heterogeneity of gene expression, which precludes the identification of defined subpopulations ...

Abstract	Bone marrow (BM) stromal cells are important in the development and maintenance of cells of the immune system. Using single cell RNA sequencing, we here explore the functional and phenotypic heterogeneity of individual transcriptomes of 1167 murine BM mesenchymal stromal cells. These cells exhibit a tremendous heterogeneity of gene expression, which precludes the identification of defined subpopulations. However, according to the expression of 108 genes involved in the communication of stromal cells with hematopoietic cells, we have identified 14 non-overlapping subpopulations, with distinct cytokine or chemokine gene expression signatures. With respect to the maintenance of subsets of immune memory cells by stromal cells, we identified distinct subpopulations expressing Il7, Il15 and Tnfsf13b. Together, this study provides a comprehensive dissection of the BM stromal heterogeneity at the single cell transcriptome level and provides a basis to understand their lifestyle and their role as organizers of niches for the long-term maintenance of immune cells.
MeSH term(s)	Animals ; B-Cell Activating Factor/genetics ; Bone Marrow/physiology ; Bone Marrow Cells/cytology ; Cells, Cultured ; Cytokines/genetics ; Hematopoietic Stem Cells/cytology ; Interleukin-15/genetics ; Interleukin-7/genetics ; Mesenchymal Stem Cells/cytology ; Mice ; Mice, Inbred C57BL ; Sequence Analysis, RNA/methods ; Stromal Cells/cytology ; Transcriptome/genetics
Chemical Substances	B-Cell Activating Factor ; Cytokines ; Interleukin-15 ; Interleukin-7
Language	English
Publishing date	2019-06-07
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.201848053
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Article ; Online: Current insights into the bone marrow niche: From biology in vivo to bioengineering ex vivo.

Xiao, Yinbo / McGuinness, ChanelleA S / Doherty-Boyd, W Sebastian / Salmeron-Sanchez, Manuel / Donnelly, Hannah / Dalby, Matthew J

Biomaterials

2022 Volume 286, Page(s) 121568

Abstract: ... immune cells. They reside primarily within the bone marrow (BM) niche microenvironment, which provides signals ... Many questions remain regarding the heterogeneity of niche components and the interactions of HSCs ... with traditional in vitro work to establish ex vivo BM niche models. These models exhibit promising potential ...

Abstract	Hematopoietic stem cells (HSCs) are fundamental to the generation of the body's blood and immune cells. They reside primarily within the bone marrow (BM) niche microenvironment, which provides signals responsible for the regulation of HSC activities. While our understanding of these signalling mechanisms continues to improve, our ability to recapitulate them in vitro to harness the clinical potential of the HSC populations is still lacking. Recent studies have applied novel engineering techniques combined with traditional in vitro work to establish ex vivo BM niche models. These models exhibit promising potential for research and clinical applications. In this review, BM niche factors that regulate the HSCs in vivo are discussed and their applications in the engineering of BM biomaterial-based platforms are considered. Many questions remain regarding the heterogeneity of niche components and the interactions of HSCs with their microenvironment. A greater understanding of the niche would help to elucidate these remaining questions, leading to the development of novel therapeutic tools.
MeSH term(s)	Bioengineering ; Biology ; Bone Marrow ; Bone Marrow Cells ; Hematopoietic Stem Cells/physiology ; Stem Cell Niche
Language	English
Publishing date	2022-05-07
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2022.121568
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Article: The Route of the Malignant Plasma Cell in Its Survival Niche: Exploring "Multiple Myelomas".

Solimando, Antonio Giovanni / Da Vià, Matteo Claudio / Bolli, Niccolò / Steinbrunn, Torsten

Cancers

2022 Volume 14, Issue 13

Abstract: ... elusive. With this review, we aim to provide an update on MM homing and resilience in the bone marrow ... in a dynamic model that customizes a given treatment to a specific patient. Genetic heterogeneity and current ...

Abstract	Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating the immune-microenvironment and have envisioned targeting these suppressive pathways to improve therapeutic outcomes. Nevertheless, some subgroups of patients include those with particularly unfavorable prognoses. Biological stratification can be used to categorize patient-, disease- or therapy-related factors, or alternatively, these biological determinants can be included in a dynamic model that customizes a given treatment to a specific patient. Genetic heterogeneity and current knowledge enforce a systematic and comprehensive bench-to-bedside approach. Given the increasing role of cancer stem cells (CSCs) in better characterizing the pathogenesis of solid and hematological malignancies, disease relapse, and drug resistance, identifying and describing CSCs is of paramount importance in the management of MM. Even though the function of CSCs is well-known in other cancer types, their role in MM remains elusive. With this review, we aim to provide an update on MM homing and resilience in the bone marrow micro milieu. These data are particularly interesting for clinicians facing unmet medical needs while designing novel treatment approaches for MM.
Language	English
Publishing date	2022-07-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14133271
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