What’s in the Offing?

Bioprinting ◽  
2021 ◽  
pp. 202-218
Author(s):  
Kenneth Douglas
Keyword(s):  
3D Printing ◽  
Cell Density ◽  
Cardiac Tissue ◽  
High Cell Density ◽  
High Density ◽  
High Cell ◽  
Hierarchical Network ◽  
Native Tissue ◽  
Vascular Channels ◽  
Cell Densities

Abstract: This chapter attempts to peer into the possible future of bioprinting to consider two conceivable directions that bioprinting might take while also contemplating what we may be able to learn about bioprinting’s trajectory by reflecting on another biomedical quest—the twentieth-century’s attempt to conquer polio. In one study that might offer a route for bioprinting, a team created bioconstructs with cell densities approaching that of native tissue (about 108 cells/gram). The group used embedded 3D printing to create a branched, hierarchical network of vascular channels within a large, high cell density bioconstruct and perfused media through the channels that they created using fugitive ink. This was to provide nutrient support for the cells. They also built a high-density cardiac construct in which the cells beat synchronously and showed functional contractility. They quantitatively measured the deformation of the cardiac tissue during contraction.

scholarly journals Chemotactic behaviour of Escherichia coli at high cell density

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Remy Colin ◽  
Knut Drescher ◽  
Victor Sourjik
Keyword(s):  
Escherichia Coli ◽  
Cell Density ◽  
Collective Motion ◽  
High Cell Density ◽  
Environmental Gradients ◽  
Model Organism ◽  
High Density ◽  
Intermediate Cell ◽  
High Cell ◽  
Cell Densities

AbstractAt high cell density, swimming bacteria exhibit collective motility patterns, self-organized through physical interactions of a however still debated nature. Although high-density behaviours are frequent in natural situations, it remained unknown how collective motion affects chemotaxis, the main physiological function of motility, which enables bacteria to follow environmental gradients in their habitats. Here, we systematically investigate this question in the model organism Escherichia coli, varying cell density, cell length, and suspension confinement. The characteristics of the collective motion indicate that hydrodynamic interactions between swimmers made the primary contribution to its emergence. We observe that the chemotactic drift is moderately enhanced at intermediate cell densities, peaks, and is then strongly suppressed at higher densities. Numerical simulations reveal that this suppression occurs because the collective motion disturbs the choreography necessary for chemotactic sensing. We suggest that this physical hindrance imposes a fundamental constraint on high-density behaviours of motile bacteria, including swarming and the formation of multicellular aggregates and biofilms.

scholarly journals Chemotactic behaviour ofEscherichia coliat high cell density

2018 ◽  
Author(s):  
Remy Colin ◽  
Knut Drescher ◽  
Victor Sourjik
Keyword(s):  
Cell Density ◽  
Collective Motion ◽  
High Cell Density ◽  
Environmental Gradients ◽  
Model Organism ◽  
High Density ◽  
Intermediate Cell ◽  
High Cell ◽  
Swimming Bacteria ◽  
Cell Densities

AbstractAt high cell density, swimming bacteria exhibit collective motility patterns, self-organized through physical interactions of a however still debated nature. Although high-density behaviours are frequent in natural situations, it remained unknown how collective motion affects chemotaxis, the main physiological function of motility, which enables bacteria to follow environmental gradients in their habitats. Here, we systematically investigate this question in the model organismEscherichia coli, varying cell density, cell length, and suspension confinement. The characteristics of the collective motion indicate that hydrodynamic interactions between swimmers made the primary contribution to its emergence. We observe that the chemotactic drift is moderately enhanced at intermediate cell densities, peaks, and is then strongly suppressed at higher densities. Numerical simulations reveal that this suppression occurs because the collective motion disturbs the choreography necessary for chemotactic sensing. We suggest that this physical hindrance imposes a fundamental constraint on high-density behaviours of motile bacteria, including swarming and the formation of multicellular aggregates and biofilms.

scholarly journals ATP Mediates Yeast Cell-Cell Communication

2020 ◽  
Author(s):  
Michael Caplow
Keyword(s):  
Cell Density ◽  
High Cell Density ◽  
Cell Communication ◽  
Growth Stimulation ◽  
High Density ◽  
Mutant Protein ◽  
Chromosome Loss ◽  
Low Density ◽  
High Cell ◽  
In Cells

AbstractYeast secrete ATP in response to glucose, a property with previously unknown functional consequence. In this report, we show that extracellular ATP is a signal for growth of surrounding cells. The ATP signaling behavior was uncovered by finding reduced toxicity of an inducible, dominant-lethal form of alpha tubulin (tub1-828) in cells grown at high, compared to low cell density. Reduced cell death at high cell density resulted because the rate of chromosome loss/cell division was lower (18-fold) in a cultures inoculated with a high density (350,000) compared to a low density (5,000) of cells. The sparing effect of growth at high cell density could be replicated by growing together 3440 cells that express tub1-828, with 2.3 E6 cells that do not express the mutant protein. Toxicity was reduced at high cell density apparently because a secreted signal induces growth, so that the mutant protein is rapidly diluted by synthesis of wild-type α-tubulin. Further, fluorescence-activated cell sorting (FACS) analysis after DNA staining showed that the rate of the G1-G2 transition was faster with cells at high density. ATP replaced the need for high cell density for resistance to tub1-828, and stimulated the transition from G1 to G2 in cells at low density. Cells lacking the enzyme nucleoside diphosphate kinase did not respond to nucleotide stimulation of growth during expression of mutant tubulin, suggesting that NDP kinase has a regulatory role in growth stimulation. This newly discovered quorum sensing response in yeast, mediated by ATP, indicates that yeast decision-making is not entirely autonomous.

scholarly journals 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andrew C. Daly ◽  
Matthew D. Davidson ◽  
Jason A. Burdick
Keyword(s):  
Cell Density ◽  
Spatial Organization ◽  
High Cell Density ◽  
Self Healing ◽  
High Cell ◽  
Cellular Models ◽  
Functional Features ◽  
Cell Densities ◽  
Tissue Models

AbstractCellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy. Current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and the screening of drugs, particularly where high cell densities and heterogeneity are important.

scholarly journals 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels

2020 ◽  
Author(s):  
Andrew C. Daly ◽  
Matthew D. Davidson ◽  
Jason A. Burdick
Keyword(s):  
Cell Density ◽  
Spatial Organization ◽  
High Cell Density ◽  
Self Healing ◽  
High Cell ◽  
Cellular Models ◽  
Functional Features ◽  
Cell Densities ◽  
Tissue Models

AbstractCellular models are needed to study human development and disease in vitro, including the screening of drugs for toxicity and efficacy. However, current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a new bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and for the screening of drugs, particularly where high cell densities and heterogeneity are important.

scholarly journals High-density preculture of PBMCs restores defective sensitivity of circulating CD8 T cells to virus- and tumor-derived antigens

Blood ◽  
2015 ◽  
Vol 126 (2) ◽  
pp. 185-194 ◽  
Author(s):  
Julia Wegner ◽  
Stephan Hackenberg ◽  
Claus-Jürgen Scholz ◽  
Sergey Chuvpilo ◽  
Dmitry Tyrsin ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Density ◽  
Cd8 T Cells ◽  
Memory T Cells ◽  
High Cell Density ◽  
High Density ◽  
High Cell ◽  
Key Points ◽  
Cd8 Memory T Cells

Key Points CD8 memory T cells in PBMCs are antigen-hyporesponsive due to loss of priming by tissue-dependent interactions. Preculture at high cell density allows the detection of antiviral and antitumor responses that may be overlooked without this step.

scholarly journals pH AND POPULATION DENSITY IN THE REGULATION OF ANIMAL CELL MULTIPLICATION

1971 ◽  
Vol 51 (3) ◽  
pp. 686-702 ◽  
Author(s):  
H. Rubin
Keyword(s):  
Cell Migration ◽  
Cell Density ◽  
Plasma Membranes ◽  
High Cell Density ◽  
Low Ph ◽  
Cell Multiplication ◽  
High Cell ◽  
High Ph ◽  
Cell Densities ◽  
Very High

Sparse and dense cultures of chick embryo cells were affected differently by pH. The rates of cell multiplication and of thymidine-3H incorporation into DNA of dense cultures were increased as the pH was increased from 6.6 to 7.6. At pH higher than 7.6 the rate of multiplication decreased slightly in the dense cultures, but the rate of thymidine-3H incorporation continued to increase. The discrepancy was due in part to cell death and detachment at very high pH, and in part to a more rapid uptake of thymidine-3H at very high pH. Sparse cultures were much less sensitive to pH reduction and, when a suitably conditioned medium was used to minimize cell damage, very sparse cultures grew almost as well at pH 6.7 as at higher pH. The rates of cell multiplication and thymidine-3H incorporation at low pH decreased in the initially sparse cultures before they reached confluent cell densities. There was no microscope evidence of direct contact between plasma membranes of cells at these densities although the parallel orientation indicated that the cells were influencing locally each other's behavior. Even at much higher cell densities, electron microscopy revealed large intercellular gaps partly filled with a fragmentary electron-opaque material suspected to be glycoprotein. Wounding experiments showed that pH affected cell migration in a manner similar to its effects on cell multiplication. Low pH inhibited cell migration, but those cells which migrated into the denuded region multiplied as rapidly at low pH as at high pH. The effects of pH on growth were correlated with effects on the uptake of 2-deoxyglucose-3H. Dense populations of cells inhibited by low pH were stimulated to incorporate thymidine-3H by the addition of small amounts of diethylaminoethyl-dextran. Rous sarcoma cells at high cell density were less sensitive to pH than were normal cells at the same density, but were more sensitive than sparse normal cultures. The results suggest that cell growth is inhibited through the combined effects of both lowered pH and high cell density on cell surface permeability.

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