The fate of the centrosome-microtubule network in monocyte-derived giant cells

1989 ◽  
Vol 94 (2) ◽  
pp. 237-244
Author(s):  
M. Moudjou ◽  
M. Lanotte ◽  
M. Bornens
Keyword(s):  
Progenitor Cells ◽  
Cell Spreading ◽  
Giant Cells ◽  
Precursor Cell ◽  
Marked Contrast ◽  
Microtubule Network ◽  
Binucleate Cells ◽  
The One ◽  
Irregular Cluster

Avian monocyte-derived giant cells in vitro, which are in many respects similar to osteoclasts, display a complex microtubule array that plays a prominent role in cell spreading. It is organized by a polygonal row of regularly spaced centrosomes surrounding an irregular cluster of nuclei. The immediate progenitor cells are binucleate cells with a single microtubule-organising center (MTOC), the result of the congregation of the two individual centrosomes. The one-to-one correspondence between numbers of centrosomes and nuclei in giant cells suggests that the centrosome of each precursor cell has been conserved through the fusion process. This is in marked contrast to the absence of centrosomes in myotubes, another example of a differentiated cell derived from the fusion of progenitor cells.

scholarly journals Regulation of proliferation of murine megakaryocyte progenitor cells by cell cycle

Blood ◽  
1978 ◽  
Vol 52 (1) ◽  
pp. 163-170 ◽  
Author(s):  
N Williams ◽  
H Jackson
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Bimodal Distribution ◽  
Precursor Cell ◽  
Proliferative Capacity ◽  
Colony Forming Unit ◽  
Regulation Of Proliferation ◽  
Modal Values

The extent to which mouse megakaryocyte progenitor cells (colony- forming unit-megakaryocyte, CFU-M) can proliferate in semisolid cultures prior to endomitosis, and conditions that may regulate that differentiation step, were investigated. The proliferative capacity of CFU-M was determined by estimating the number of megakaryocytes per colony. A bimodal distribution was observed (modal values, 10–15 and 25- 30 cells/colony), indicating that separate megakaryocyte progenitor cells may be biased in their capacity for proliferation versus endomitosis. Differences were observed in the cell cycle characteristics of CFU-M as determined in vivo and in vitro that suggest that maturation of CFU-M into megakaryocytes may be regulated within the marrow by control of the cell cycle of the megakaryocyte precursor cell.

scholarly journals CD13 is a Critical Regulator of Cell-cell Fusion in Osteoclastogenesis

2020 ◽  
Author(s):  
Mallika Ghosh ◽  
Ivo Kalajzic ◽  
Hector Leonardo Aguila ◽  
Linda H Shapiro
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Progenitor Cells ◽  
Cell Fusion ◽  
Formation Rate ◽  
Giant Cells ◽  
Bone Formation Rate ◽  
Cell Cell

AbstractIn vertebrates, bone formation is dynamically controlled by the activity of two specialized cell types: the bone-generating osteoblasts and bone-degrading osteoclasts. Osteoblasts produce the soluble receptor activator of NFκB ligand (RANKL) that binds to its receptor RANK on the surface of osteoclast precursor cells to promote osteoclastogenesis, a process that involves cell-cell fusion and assembly of molecular machinery to ultimately degrade the bone. CD13 is a transmembrane aminopeptidase that is highly expressed in cells of myeloid lineage has been shown to regulate dynamin-dependent receptor endocytosis and recycling and is a necessary component of actin cytoskeletal organization. In the present study, we show that CD13-deficient mice display a normal distribution of osteoclast progenitor populations in the bone marrow, but present a low bone density phenotype. Further, the endosteal bone formation rate is similar between genotypes, indicating a defect in osteoclast-specific function in vivo. Loss of CD13 led to exaggerated in vitro osteoclastogenesis as indicated by significantly enhanced fusion of bone marrow-derived multinucleated osteoclasts in the presence of M-CSF and RANKL, resulting in abnormally large cells with remarkably high numbers of nuclei with a concomitant increase in bone resorption activity. Similarly, we also observed increased formation of multinucleated giant cells (MGC) in CD13KO bone marrow progenitor cells stimulated with IL-4 and IL-13, suggesting that CD13 may regulate cell-cell fusion events via a common pathway, independent of RANKL signaling. Mechanistically, while expression levels of the fusion-regulatory proteins dynamin and DC-STAMP are normally downregulated as fusion progresses in fusion-competent mononucleated progenitor cells, in the absence of CD13 they are uniformly sustained at high levels, even in mature multi-nucleated osteoclasts. Taken together, we conclude that CD13 may regulate cell-cell fusion by controlling expression and localization of key fusion proteins that are critical for both osteoclast and MGC fusion.

Lysosomes and the "toxicity" of Rickettsials. II. Non-cytocidal interactions of egg-grown C. psittaci 6BC and in vitro macrophages

1972 ◽  
Vol 18 (6) ◽  
pp. 869-873 ◽  
Author(s):  
Nonna Kordová ◽  
Linda Poffenroth ◽  
John C. Wilt
Keyword(s):  
Acid Phosphatase ◽  
Cell Damage ◽  
Giant Cells ◽  
Host Cells ◽  
Marked Contrast ◽  
Lysosomal Acid ◽  
Cytoplasmic Vacuoles ◽  
L Cell

During the infection of cultured mouse peritoneal phagocytes with egg-grown C. psittaci 6BC strain, lysosomes retained their integrity and host cells were not damaged. Infected monocytes showed greater ability than uninfected monocytes to spread and transform into giant cells containing enlarged nuclei and masses of cytoplasm with clear cytoplasmic vacuoles. Chlamydial particles were released from the cytoplasm of infected phagocytes by pseudopodia-like extrusions. These events were in marked contrast to the effect of L cell grown C. psittaci 6BC strain which caused early leakage of lysosomal acid phosphatase into the cytoplasm of macrophages and induced a rapidly progressive irreversible cell damage (14).

scholarly journals Regulation of proliferation of murine megakaryocyte progenitor cells by cell cycle

Blood ◽  
1978 ◽  
Vol 52 (1) ◽  
pp. 163-170 ◽  
Author(s):  
N Williams ◽  
H Jackson
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Bimodal Distribution ◽  
Precursor Cell ◽  
Proliferative Capacity ◽  
Colony Forming Unit ◽  
Regulation Of Proliferation ◽  
Modal Values

Abstract The extent to which mouse megakaryocyte progenitor cells (colony- forming unit-megakaryocyte, CFU-M) can proliferate in semisolid cultures prior to endomitosis, and conditions that may regulate that differentiation step, were investigated. The proliferative capacity of CFU-M was determined by estimating the number of megakaryocytes per colony. A bimodal distribution was observed (modal values, 10–15 and 25- 30 cells/colony), indicating that separate megakaryocyte progenitor cells may be biased in their capacity for proliferation versus endomitosis. Differences were observed in the cell cycle characteristics of CFU-M as determined in vivo and in vitro that suggest that maturation of CFU-M into megakaryocytes may be regulated within the marrow by control of the cell cycle of the megakaryocyte precursor cell.

Human thymic epithelial cells maintain long-term survival of clonogenic myeloid and erythroid progenitor cells in vitro

2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Progenitor Cells ◽  
Thymic Epithelial Cells ◽  
Erythroid Progenitor ◽  
Term Survival ◽  
Long Term Survival ◽  
Erythroid Progenitor Cells

Gene transfer of endothelial NO-synthase restores migratory capacity of endothelial progenitor cells from patients with coronary artery diseases

2007 ◽  
Vol 30 (4) ◽  
pp. 96
Author(s):  
Michael R. Ward ◽  
Qiuwang Zhang ◽  
Duncan J. Stewart ◽  
Michael J.B. Kutryk
Keyword(s):  
Risk Factors ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Fold Increase ◽  
No Synthase ◽  
Endothelial Progenitor ◽  
Migratory Capacity ◽  
Acute Mi ◽  
Cad Risk

Autologous endothelial progenitor cells (EPCs) have been used extensively in the development of cell-based therapy for acute MI. However, EPCs isolated from patients with CAD and/or CAD risk factors have reduced regenerative activity compared to cells from healthy subjects. As in endothelial cells, endothelial NO synthase (eNOS) expression and subsequent NO production are believed to be critical determinants of EPC function. Recently, the ability of EPCs to migrate in vitro in response to chemotactic stimuli has been shown to predict their regenerative capacity in clinical studies. Therefore, we hypothesized that the regenerative function of EPCs from patients with or at high risk for CAD will be enhanced by overexpression of eNOS, as assessed by migratory capacity. Methods: EPCs were isolated from the blood of human subjects with CAD risk factors (>15% Framingham risk score; FRS) (± CAD) by Ficoll gradient separation and differential culture. Following 3 days in culture, cells were transduced using lentivirus vectors containing either eNOS or GFP (sham) at an MOI of 3. The cells were cultured for an additional 5 days before being used in functional assays. Cell migration and chemotaxis in response to VEGF (50 ng/mL) and SDF-1 (100 ng/mL) were assessed using a modified Boyden Chamber assay. Results: Transduction at an MOI of 3 led to a ~90-100-fold increase in eNOS mRNA expression and a 5-6 fold increase in eNOS protein expression, as assessed by qRT-PCR and Western Blotting. Moreover, there was a significant improvement in the migration of EPCs following eNOS transduction compared to sham-transduced EPCs in response to both VEGF (44.3 ± 8.4 vs. 31.1 ± 4.6 cells/high power field; n=10, p < 0.05) and SDF-1 (51.9 ± 11.1 vs. 34.5 ± 3.3 cells/HPF; n=10, p < 0.05). Conclusions: These data show that the reduced migration capacity of EPCs isolated from patients with CAD and/or CAD risk factors can be significantly improved through eNOS overexpression in these cells. Thus, eNOS transduction of autologous EPCs may enhance their ability to restore myocardial perfusion and function following acute MI. We intend to further explore the regenerative potential of eNOS-transduced EPCs using various in vitro and in vivo models.

Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Marietta Herrmann ◽  
Franz Jakob
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Cell Populations ◽  
Surface Markers ◽  
Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

scholarly journals Immune regulation of in vitro murine megakaryocyte development. Role of T lymphocytes and Ia antigen expression.

1985 ◽  
Vol 162 (6) ◽  
pp. 2053-2067 ◽  
Author(s):  
M W Long ◽  
D N Shapiro
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
T Lymphocytes ◽  
Progenitor Cells ◽  
Immune Modulation ◽  
Immune Recognition ◽  
Activated T Cells ◽  
Ia Antigen ◽  
Cell Cycle Status

Mitogen-activated murine T lymphocytes or T cell hybridomas produce an activity (megakaryocyte [Mk] potentiator activity) that enhances the in vitro growth and development of Mk colonies. This activity was found in optimal concentrations (2.5%) in T cell hybridoma-conditioned medium, and was also produced by feeder layers of concanavalin A-activated T cells. A subpopulation of murine Mk progenitor cells (colony-forming units; CFU-Mk) bears the Ia antigen. Separate experiments indicated that T cell products stimulate CFU-Mk by increasing their basal levels of Ia expression as well as the frequency of cells actively synthesizing DNA. The hypothesis that the expression of this antigen was related to the cell cycle status of these progenitor cells was confirmed in studies that indicated that ablation of actively cycling cells in vivo abrogated the cytotoxic effects of anti-Ia monoclonal antibodies. The interdependence of T cell lymphokine regulation of both Ia expression and cell cycle status was also seen in in vitro experiments in which Ia+ progenitor cells were eliminated by complement-dependent cytotoxicity. The removal of Ia+ cells prevented 5-hydroxyurea-mediated inhibition of cells in S phase. We hypothesize that immune modulation of megakaryocytopoiesis occurs via soluble T cell products that augment Mk differentiation. Further, the mechanism of immune recognition/modulation may occur via Ia antigens present on the surface of these progenitor cells.

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