scholarly journals Faulty ribosomes and human diseases: mistakes in “assembly line” going unnoticed ?

2015 ◽  
Vol 05 (03) ◽  
pp. 087-092
Author(s):  
Anirban Chakraborty ◽  
Indrani Karunasagar
Keyword(s):  
Bone Marrow ◽  
Assembly Line ◽  
Clinical Symptoms ◽  
Genetic Disorders ◽  
Living Organism ◽  
Cell Types ◽  
Human Embryos ◽  
Ribosome Assembly ◽  
Specific Cell ◽  
Specific Nature

AbstractRibosomes are molecular machineries that decode the information within mRNAs and generate all the proteins required for cellular activities. Ribosomes are essential to every living organism. The synthesis of ribosome is an intricate process, which is carried out in multiple steps throughout the cell in a highly coordinated fashion. For many years, the general perception was that any defects in the “ribosome assembly line” would have fatal consequences on cell. However, it has now become clear that production of defective ribosomes does not lead to lethality in human embryos. Rather, it manifests as specific disease conditions called ribosomopathies, which are rare genetic disorders affecting the bone marrow. This group of diseases has received considerable attention in recent years because of the mystery associated with them i.e. the tissue-specific nature of the clinical phenotypes despite the fact that the genes mutated in patients code for proteins that are absolutely essential and are housekeeping in nature. Despite considerable progress in understanding these diseases, it still remains unclear why defects in the production of a macromolecule as indispensable and as ubiquitous as the ribosome go unnoticed and why the effects are not universal but rather are restricted to specific cell types. This review is aimed at introducing the readers to important ribosomopathies with a brief description about the clinical symptoms, molecular genetics, and the treatments strategies.

scholarly journals Immunomagnetic Isolation of Rat Bone Marrow-derived and Peritoneal Mast Cells

1997 ◽  
Vol 45 (12) ◽  
pp. 1715-1722 ◽  
Author(s):  
Maria Celia Jamur ◽  
Ana Cristina G. Grodzki ◽  
Andrea N. Moreno ◽  
William D. Swaim ◽  
Reuben P. Siraganian ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Cell Types ◽  
Ultrastructural Level ◽  
Immunomagnetic Separation ◽  
Specific Cell ◽  
Morphological Examination ◽  
Immunomagnetic Isolation ◽  
Rat Bone

Mast cells are difficult to purify from heterogeneous cell populations and to preserve, especially for pre-embedding immunostaining at the ultrastructural level. We have developed a technique that permits the isolation of a pure population of mast cells suitable for immunocytochemical studies. A rat mast cell-specific monoclonal antibody (MAb AA4) conjugated to tosylactivated Dynabeads 450 was used to immunomagnetically separate mast cells from rat bone marrow and peritoneal cell suspensions. Approximately 85% of the mast cells were recovered in the positive population that comprised virtually pure mast cells. After microwave fixation, morphological examination showed that the cells were intact and retained their ultrastructural detail. Mast cells in all stages of maturation were immunolabeled with a panel of antibodies after immunomagnetic separation. The combination of immunomagnetic separation followed by immunostaining should prove useful for the study of mast cell maturation and for the characterization of other specific cell types that are present in tissues in only limited numbers.

scholarly journals The atypical chemokine receptor ACKR2 drives pulmonary fibrosis by tuning influx of CCR2+ and CCR5+ IFNγ-producing γδT cells in mice

2018 ◽  
Vol 314 (6) ◽  
pp. L1010-L1025 ◽  
Author(s):  
Remo C. Russo ◽  
Benedetta Savino ◽  
Massimiliano Mirolo ◽  
Chiara Buracchi ◽  
Giovanni Germano ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pulmonary Fibrosis ◽  
Chemokine Receptors ◽  
Clinical Symptoms ◽  
Cell Types ◽  
Th17 Response ◽  
Γδt Cells ◽  
Leukocyte Influx ◽  
Bone Marrow Chimeras

Chemokines coordinate lung inflammation and fibrosis by acting on chemokine receptors expressed on leukocytes and other cell types. Atypical chemokine receptors (ACKRs) bind, internalize, and degrade chemokines, tuning homeostasis and immune responses. ACKR2 recognizes and decreases the levels of inflammatory CC chemokines. The role of ACKR2 in fibrogenesis is unknown. The purpose of the study was to investigate the role of ACKR2 in the context of pulmonary fibrosis. The effects of ACKR2 expression and deficiency during inflammation and fibrosis were analyzed using a bleomycin-model of fibrosis, ACKR2-deficient mice, bone marrow chimeras, and antibody-mediated leukocyte depletion. ACKR2 was upregulated acutely in response to bleomycin and normalized over time. ACKR2−/− mice showed reduced lethality and lung fibrosis. Bone marrow chimeras showed that lethality and fibrosis depended on ACKR2 expression in pulmonary resident (nonhematopoietic) cells but not on leukocytes. ACKR2−/− mice exhibited decreased expression of tissue-remodeling genes, reduced leukocyte influx, pulmonary injury, and dysfunction. ACKR2−/− mice had early increased levels of CCL5, CCL12, CCL17, and IFNγ and an increased number of CCR2+ and CCR5+ IFNγ-producing γδT cells in the airways counterbalanced by low Th17-lymphocyte influx. There was reduced accumulation of IFNγ-producing γδT cells in CCR2−/− and CCR5−/− mice. Moreover, depletion of γδT cells worsened the clinical symptoms induced by bleomycin and reversed the phenotype of ACKR2−/− mice exposed to bleomycin. ACKR2 controls the CC chemokine expression that drives the influx of CCR2+ and CCR5+ IFNγ-producing γδT cells, tuning the Th17 response that mediated pulmonary fibrosis triggered by bleomycin instillation.

scholarly journals Estradiol Synthesis and Release in Cultured Female Rat Bone Marrow Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Dalei Zhang ◽  
Bei Yang ◽  
Weiying Zou ◽  
Xiaying Lu ◽  
Mingdi Xiong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
De Novo ◽  
Autologous Transplantation ◽  
Cell Types ◽  
Culture Conditions ◽  
Bone Marrow Stem Cells ◽  
Specific Cell ◽  
Female Rat ◽  
Alternative Source

Bone marrow stem cells (BMSCs) have the capacity to differentiate into mature cell types of multiple tissues. Thus, they represent an alternative source for organ-specific cell replacement therapy in degenerative diseases. In this study, we demonstrated that female rat BMSCs could differentiate into steroidogenic cells with the capacity forde novosynthesis of Estradiol-17β(E2) under high glucose culture conditions with or without retinoic acid (RA). The cultured BMSCs could express the mRNA and protein for P450arom, the enzyme responsible for estrogen biosynthesis. Moreover, radioimmunoassay revealed that BMSCs cultured in the present culture system produced and secreted significant amounts of testosterone, androstenedione, and E2. In addition, RA promoted E2 secretion but did not affect the levels of androgen. These results indicate that BMSCs can synthesize and release E2 and may contribute to autologous transplantation therapy for estrogen deficiency.

scholarly journals Tissue specific targeting of DNA nanodevices in a multicellular living organism

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kasturi Chakraborty ◽  
Palapuravan Anees ◽  
Sunaina Surana ◽  
Simona Martin ◽  
Jihad Aburas ◽  
...  
Keyword(s):  
Living Organism ◽  
Cell Types ◽  
Specific Cell ◽  
Full Potential ◽  
Tissue Specific ◽  
C Elegans ◽  
Specific Targeting ◽  
Synthetic Receptor ◽  
Ligand Interactions

Nucleic acid nanodevices present great potential as agents for logic-based therapeutic intervention as well as in basic biology. Often, however, the disease targets that need corrective action are localized in specific organs and thus realizing the full potential of DNA nanodevices also requires ways to target them to specific cell-types in vivo. Here we show that by exploiting either endogenous or synthetic receptor-ligand interactions and by leveraging the biological barriers presented by the organism, we can target extraneously introduced DNA nanodevices to specific cell types in C. elegans, with sub-cellular precision. The amenability of DNA nanostructures to tissue-specific targeting in vivo significantly expands their utility in biomedical applications and discovery biology.

scholarly journals Cerebral organoids: ethical issues and consciousness assessment

2018 ◽  
Vol 44 (9) ◽  
pp. 606-610 ◽  
Author(s):  
Andrea Lavazza ◽  
Marcello Massimini
Keyword(s):  
Ethical Issues ◽  
Personalised Medicine ◽  
Three Dimensional ◽  
Cell Types ◽  
Human Embryos ◽  
Specific Cell ◽  
Neural Connections ◽  
Structural And Functional Properties ◽  
Organ Specific

Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and pathologies of human cells; they also make it possible to test new molecules on human tissue. Furthermore, organoids have helped research take a step forward in the field of personalised medicine and transplants. However, some ethical issues have arisen concerning the origin of the cells that are used to produce organoids (ie, human embryos) and their properties. In particular, there are new, relevant and so-far overlooked ethical questions concerning cerebral organoids. Scientists have created so-called mini-brains as developed as a few-months-old fetus, albeit smaller and with many structural and functional differences. However, cerebral organoids exhibit neural connections and electrical activity, raising the question whether they are or (which is more likely) will one day be somewhat sentient. In principle, this can be measured with some techniques that are already available (the Perturbational Complexity Index, a metric that is directly inspired by the main postulate of the Integrated Information Theory of consciousness), which are used for brain-injured non-communicating patients. If brain organoids were to show a glimpse of sensibility, an ethical discussion on their use in clinical research and practice would be necessary.

scholarly journals A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2841-2848 ◽  
Author(s):  
Y Deguchi ◽  
A Kirschenbaum ◽  
JH Kehrl
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Homeobox Gene ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Specific Cell ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells ◽  
Acute Myelogenous

HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c- fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

Spatial Analysis of Hematopoietic Stem and Progenitor Cells in the Bone Marrow

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3570-3570
Author(s):  
Cesar Nombela-Arrieta ◽  
Brendan Harley ◽  
Elena Levantini ◽  
John E Mahoney ◽  
Gregory Pivarnik ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Laser Scanning ◽  
Imaging Techniques ◽  
Cell Types ◽  
Specific Cell ◽  
Hematopoietic Stem ◽  
Lineage Differentiation ◽  
Stem And Progenitor Cells ◽  
Laser Scanning Cytometry

Abstract Sustained production of all mature blood cell types relies on the continuous proliferation and differentiation of a rare population of self-renewing, multipotent hematopoietic stem cells (HSCs). HSC maintenance and lineage differentiation are strictly regulated by distinct microenvironments, termed niches, defined by cellular components, soluble regulators, and by the extracellular matrix. Definitive identification of the location as well as cellular and extracellular characteristics of HSC niches in the bone marrow (BM) has not been completed due to limitations of conventional imaging techniques. We have employed a novel imaging technology, Laser Scanning Cytometry (LSC) to define the localization of hematopoietic stem and progenitor cells (HSPCs) within different regions of the BM. LSC allows imaging and objective quantitative analysis of the anatomical position(s), number, and frequency of specific cell populations within the native tissue microenvironment. Analysis of whole femoral longitudinal sections of Bmi-GFP mice, in which GFP is expressed at its highest levels in HSPCs, revealed that within the bone diaphysis, HSPCs (Bmi-GFPhi c-kit+) cells were highly enriched in endosteal regions (within 100nm away from inner bone surface) compared to the central medullary region. Importantly, our data show that HSPCs are found at highest frequencies in the metaphysis of long bones, suggesting that these areas, which display characteristic morphological features, are functionally distinct from the diaphyseal region and a preferential location for HSPC-specific niches. We are currently employing LSC to identify HSPC niche cellular constituents by quantifying the relative frequency at which these cells are found in association with previously proposed niche-components such as osteoblasts, BM endothelial sinusoidal cells and CXCL12-abundant reticular cells. A detailed understanding of niche-derived signals regulating unique properties of HSCs will certainly prove relevant in human HSPC transplantation and cell therapy.

scholarly journals Tissue specific targeting of DNA nanodevices in a multicellular living organism

2021 ◽  
Author(s):  
Kasturi Chakraborty ◽  
Sunaina Surana ◽  
Simona Martin ◽  
Jihad Aburas ◽  
Sandrine Moutel ◽  
...  
Keyword(s):  
Living Organism ◽  
Cell Types ◽  
Specific Cell ◽  
Full Potential ◽  
Tissue Specific ◽  
C Elegans ◽  
Specific Targeting ◽  
Synthetic Receptor ◽  
Ligand Interactions

AbstractNucleic acid nanodevices present great potential as agents for logic-based therapeutic intervention as well as in basic biology. Often, however, the disease targets that need corrective action are localized in specific organs and thus realizing the full potential of DNA nanodevices also requires ways to target them to specific cell-types in vivo. Here we show that by exploiting either endogenous or synthetic receptor-ligand interactions and by leveraging the biological barriers presented by the organism, we can target extraneously introduced DNA nanodevices to specific cell types in C. elegans, with sub-cellular precision. The amenability of DNA nanostructures to tissue-specific targeting in vivo significantly expands their utility in biomedical applications and discovery biology.

Cell therapy in orthopaedics

2019 ◽  
Vol 101-B (4) ◽  
pp. 361-364 ◽  
Author(s):  
S. A. Rodeo
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Bone Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Cell Therapies ◽  
Native Bone ◽  
Wide Range

Stem cells are defined by their potential for self-renewal and the ability to differentiate into numerous cell types, including cartilage and bone cells. Although basic laboratory studies demonstrate that cell therapies have strong potential for improvement in tissue healing and regeneration, there is little evidence in the scientific literature for many of the available cell formulations that are currently offered to patients. Numerous commercial entities and ‘regenerative medicine centres’ have aggressively marketed unproven cell therapies for a wide range of medical conditions, leading to sometimes indiscriminate use of these treatments, which has added to the confusion and unpredictable outcomes. The significant variability and heterogeneity in cell formulations between different individuals makes it difficult to draw conclusions about efficacy. The ‘minimally manipulated’ preparations derived from bone marrow and adipose tissue that are currently used differ substantially from cells that are processed and prepared under defined laboratory protocols. The term ‘stem cells’ should be reserved for laboratory-purified, culture-expanded cells. The number of cells in uncultured preparations that meet these defined criteria is estimated to be approximately one in 10 000 to 20 000 (0.005% to 0.01%) in native bone marrow and 1 in 2000 in adipose tissue. It is clear that more refined definitions of stem cells are required, as the lumping together of widely diverse progenitor cell types under the umbrella term ‘mesenchymal stem cells’ has created confusion among scientists, clinicians, regulators, and our patients. Validated methods need to be developed to measure and characterize the ‘critical quality attributes’ and biological activity of a specific cell formulation. It is certain that ‘one size does not fit all’ – different cell formulations, dosing schedules, and culturing parameters will likely be required based on the tissue being treated and the desired biological target. As an alternative to the use of exogenous cells, in the future we may be able to stimulate the intrinsic vascular stem cell niche that is known to exist in many tissues. The tremendous potential of cell therapy will only be realized with further basic, translational, and clinical research. Cite this article: Bone Joint J 2019;101-B:361–364.

scholarly journals A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2841-2848 ◽  
Author(s):  
Y Deguchi ◽  
A Kirschenbaum ◽  
JH Kehrl
Keyword(s):  
Bone Marrow ◽  
Acute Myelogenous Leukemia ◽  
Homeobox Gene ◽  
Cell Types ◽  
Myelogenous Leukemia ◽  
Specific Cell ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells ◽  
Acute Myelogenous

Abstract HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c- fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

Sign in / Sign up

Export Citation Format

Share Document