scholarly journals 3D Bioprinted Spheroidal Droplets for Engineering the Heterocellular Coupling between Cardiomyocytes and Cardiac Fibroblasts

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Raven El Khoury ◽  
Naveen Nagiah ◽  
Joel A. Mudloff ◽  
Vikram Thakur ◽  
Munmun Chattopadhyay ◽  
...  

Since conventional human cardiac two-dimensional (2D) cell culture and multilayered three-dimensional (3D) models fail in recapitulating cellular complexity and possess inferior translational capacity, we designed and developed a high-throughput scalable 3D bioprinted cardiac spheroidal droplet-organoid model with cardiomyocytes and cardiac fibroblasts that can be used for drug screening or regenerative engineering applications. This study helped establish the parameters for bioprinting and cross-linking a gelatin-alginate-based bioink into 3D spheroidal droplets. A flattened disk-like structure developed in prior studies from our laboratory was used as a control. The microstructural and mechanical stability of the 3D spheroidal droplets was assessed and was found to be ideal for a cardiac scaffold. Adult human cardiac fibroblasts and AC16 cardiomyocytes were mixed in the bioink and bioprinted. Live-dead assay and flow cytometry analysis revealed robust biocompatibility of the 3D spheroidal droplets that supported the growth and proliferation of the cardiac cells in the long-term cultures. Moreover, the heterocellular gap junctional coupling between the cardiomyocytes and cardiac fibroblasts further validated the 3D cardiac spheroidal droplet model.

1999 ◽  
Vol 81 (3) ◽  
pp. 1274-1283 ◽  
Author(s):  
F. K. Skinner ◽  
L. Zhang ◽  
J. L. Perez Velazquez ◽  
P. L. Carlen

Bursting in inhibitory interneuronal networks: a role for gap-junctional coupling. Much work now emphasizes the concept that interneuronal networks play critical roles in generating synchronized, oscillatory behavior. Experimental work has shown that functional inhibitory networks alone can produce synchronized activity, and theoretical work has demonstrated how synchrony could occur in mutually inhibitory networks. Even though gap junctions are known to exist between interneurons, their role is far from clear. We present a mechanism by which synchronized bursting can be produced in a minimal network of mutually inhibitory and gap-junctionally coupled neurons. The bursting relies on the presence of persistent sodium and slowly inactivating potassium currents in the individual neurons. Both GABAA inhibitory currents and gap-junctional coupling are required for stable bursting behavior to be obtained. Typically, the role of gap-junctional coupling is focused on synchronization mechanisms. However, these results suggest that a possible role of gap-junctional coupling may lie in the generation and stabilization of bursting oscillatory behavior.


2016 ◽  
Vol 594 (19) ◽  
pp. 5695-5710 ◽  
Author(s):  
Denise Kohmann ◽  
Annika Lüttjohann ◽  
Thomas Seidenbecher ◽  
Philippe Coulon ◽  
Hans-Christian Pape

Neuroscience ◽  
2001 ◽  
Vol 105 (3) ◽  
pp. 579-587 ◽  
Author(s):  
R Köhling ◽  
S.J Gladwell ◽  
E Bracci ◽  
M Vreugdenhil ◽  
J.G.R Jefferys

2000 ◽  
Vol 20 (2) ◽  
pp. 674-684 ◽  
Author(s):  
Qiang Chang ◽  
Alberto Pereda ◽  
Martin J. Pinter ◽  
Rita J. Balice-Gordon

2016 ◽  
Vol 468 (7) ◽  
pp. 1215-1222 ◽  
Author(s):  
Alexander Blödow ◽  
Daniela Begandt ◽  
Almke Bader ◽  
Annegret Becker ◽  
Alice Burghard ◽  
...  

2001 ◽  
Vol 281 (3) ◽  
pp. C972-C981 ◽  
Author(s):  
Grant C. Churchill ◽  
Monica M. Lurtz ◽  
Charles F. Louis

The quantitative effects of Ca2+signaling on gap junctional coupling in lens epithelial cells have been determined using either the spread of Mn2+ that is imaged by its ability to quench the fluorescence of fura 2 or the spread of the fluorescent dye Alexa Fluor 594. Gap junctional coupling was unaffected by a mechanically stimulated cell-to-cell Ca2+wave. Furthermore, when cytosolic Ca2+ concentration (Ca[Formula: see text]) increased after the addition of the agonist ATP, coupling was unaffected during the period that Ca[Formula: see text] was maximal. However, coupling decreased transiently ∼5–10 min after agonist addition when Ca[Formula: see text] returned to resting levels, indicating that this transient decrease in coupling was unlikely due to a direct action of Ca[Formula: see text] on gap junctions. An increase in Ca[Formula: see text] mediated by the ionophore ionomycin that was sustained for several minutes resulted in a more rapid and sustained decrease in coupling (IC50 ∼300 nM Ca2+, Hill coefficient of 4), indicating that an increase in Ca[Formula: see text]alone could regulate gap junctions. Thus Ca[Formula: see text]increases that occurred during agonist stimulation and cell-to-cell Ca2+ waves were too transient to mediate a sustained uncoupling of lens epithelial cells.


Sign in / Sign up

Export Citation Format

Share Document