ec growth factors  (ATCC)

Journal: bioRxiv

Article Title: Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease

doi: 10.1101/2024.03.15.585249

Figure Lengend Snippet: (A) Schematic of the EC network model where each white box represents a specific signaling node (i.e., protein, transcription factor, or gene), and each yellow box represents a cell fate state change. (B) Schematic of the pericyte network model where each white box represents a specific signaling node (i.e., protein, transcription factor, or gene) and each yellow box represents a cell fate state change. (C) Predictions made by the EC network model (“Model” column) about the cell fate outcomes resulting from six cellular and environmental perturbations relevant to IPF, including high56 and low VEGF57, contact with a neighboring pericyte (pericyte presence)58, 59, high TGFβ60, contact with a neighboring tip EC (presence of external DLL4)61, and high FGF41, 56. Model predictions were compared to published experiments not used for model development (“Exp” column). There was agreement between model predictions and experimental outputs for 12/14, or 85%, of the tested perturbations. (D) Predictions made by the pericyte network model (“Model” column) about the cell fate outcomes resulting from eight cellular and environmental perturbations relevant to IPF, including high concentrations of PDGF-BB62, 63, pericyte contact with a neighboring EC64, 65, high ECM stiffness43, 66, high FGF & contact with an EC (EC presence)41, 56, high concentrations of TGFβ67, 68, TGFβ inhibitor43, a combination TGFβ inhibitor and high ECM stiffness43, and a PDGF inhibitor69, 70. Model predictions were compared to published experiments (“Exp” column). There was agreement between model predictions and experimental outputs for 9/9, or 100%, of the tested perturbations.

Article Snippet: PEGylation of peptides and growth factors PEG hydrogels were functionalized with the following peptides and proteins purchased from Genscript (Piscataway, NJ): RGDS, a fibronectin-derived adhesion ligand, GGGPQGIWGQGK (PQ), a protease-sensitive degradable linker, basic fibroblast growth factor (FGF-2), an angiogenic endothelial cell mitogen, and platelet-derived growth factor (PDGF) which also contributes to angiogenic signaling in ECs and pericytes.

Techniques:

Journal: bioRxiv

Article Title: Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease

doi: 10.1101/2024.03.15.585249

Figure Lengend Snippet: (A) At 2 kPa, there is an initial reduction (below 95%) in the percentage of ECs that are in a quiescent state, but by Day 3 the percentage of ECs in a quiescent state returned to 95% or greater. (B) Pericytes at 2 kPa maintain a similar level of quiescence, with the mean remaining above the 95% quiescent threshold. (C) At 10 kPa the initial drop in the percentage of quiescent ECs was accompanied by an increase in both angiogenic and apoptotic ECs, but returned to steady state on Day 5. (D) At 10 kPa there is a decline in pericyte quiescent overtime combined with an increase in migratory pericytes and pericytes undergoing PMT. (E) At 20 kPa there is a sharp decline in quiescent ECs and increase in apoptotic ECs but the cells quickly return to a 95% quiescent steady state at Day 1. (F) The percentage of quiescent pericytes declines rapidly, dropping below 95%, starting on Day 1. On Day 1 pericytes are predicted to begin exhibiting a PMT state. N = 5, shading represents 95% confidence interval.

Article Snippet: PEGylation of peptides and growth factors PEG hydrogels were functionalized with the following peptides and proteins purchased from Genscript (Piscataway, NJ): RGDS, a fibronectin-derived adhesion ligand, GGGPQGIWGQGK (PQ), a protease-sensitive degradable linker, basic fibroblast growth factor (FGF-2), an angiogenic endothelial cell mitogen, and platelet-derived growth factor (PDGF) which also contributes to angiogenic signaling in ECs and pericytes.

Techniques:

Journal: bioRxiv

Article Title: Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease

doi: 10.1101/2024.03.15.585249

Figure Lengend Snippet: (A) Diagram of how nintedanib targets VEGFR, PDGFR, and FGFR (B) Overview of mechanistic subnetwork analysis (C) Sub-network analysis of nintedanib regulation of EC phenotype reveals quiescence is regulated in a VEGFR dependent manner alone while angiogenesis is controlled by both VEGFR and FGFR. (D) Sub-network analysis of pericyte response to nintedanib reveals FGFR is key regulator of both quiescence and migration in pericytes while PDGFR plays a strong role in maintaining pericyte quiescence. Sub-figure A was created using Biorender.com.

Article Snippet: PEGylation of peptides and growth factors PEG hydrogels were functionalized with the following peptides and proteins purchased from Genscript (Piscataway, NJ): RGDS, a fibronectin-derived adhesion ligand, GGGPQGIWGQGK (PQ), a protease-sensitive degradable linker, basic fibroblast growth factor (FGF-2), an angiogenic endothelial cell mitogen, and platelet-derived growth factor (PDGF) which also contributes to angiogenic signaling in ECs and pericytes.

Techniques: Migration

Journal: bioRxiv

Article Title: Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease

doi: 10.1101/2024.03.15.585249

Figure Lengend Snippet: (A) An IF image of healthy lung was use to prescribe initial locations for simulated ECs (red, CD31) and pericytes (purple, TdTomato Myh11 Cre labelled) in the ABM environment in NetLogo (B). (C) The logic-based network models representing ECs and pericytes were connected to the ABM environment using the Py extension in NetLogo.

Article Snippet: PEGylation of peptides and growth factors PEG hydrogels were functionalized with the following peptides and proteins purchased from Genscript (Piscataway, NJ): RGDS, a fibronectin-derived adhesion ligand, GGGPQGIWGQGK (PQ), a protease-sensitive degradable linker, basic fibroblast growth factor (FGF-2), an angiogenic endothelial cell mitogen, and platelet-derived growth factor (PDGF) which also contributes to angiogenic signaling in ECs and pericytes.

Techniques:

Journal: bioRxiv

Article Title: Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease

doi: 10.1101/2024.03.15.585249

Figure Lengend Snippet: (A) At 2 kPa an initial decrease in the percentage of quiescent ECs is accompanied by an increase in angiogenic ECs before returning to a 95% quiescent steady state. (B) The pericytes at 2 kPa overall maintain a steady state of over 95% quiescent, with the occasional spike in the percent of migratory pericytes. (C) At 10 kPa the initial drop in quiescent ECs was accompanied by an increase in both angiogenic and apoptotic ECs resulting in a delayed response to 95% quiescent steady state. (D) At 10 kPa there is still an overall pericyte steady state of above 95% quiescent cells but with an increase in the occurrence of migratory pericytes. (E) At 20 kPa a sharp decline in quiescent ECs is due to an increase in apoptosis but a quick return to a 95% quiescent steady state. (F) The percent of quiescent pericytes declines throughout the time course at 20 kPa and is associated with an increase in the percent of migratory pericytes and the occurrence of PMT. N = 5, shading represents 95% confidence interval.

Article Snippet: PEGylation of peptides and growth factors PEG hydrogels were functionalized with the following peptides and proteins purchased from Genscript (Piscataway, NJ): RGDS, a fibronectin-derived adhesion ligand, GGGPQGIWGQGK (PQ), a protease-sensitive degradable linker, basic fibroblast growth factor (FGF-2), an angiogenic endothelial cell mitogen, and platelet-derived growth factor (PDGF) which also contributes to angiogenic signaling in ECs and pericytes.

Techniques:

Journal: bioRxiv

Article Title: Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease

doi: 10.1101/2024.03.15.585249

Figure Lengend Snippet: (A) At 10 kPa treatment with a combination of nintedanib and a YAP/TAZ inhibitor results in a initial drop in EC quiescence that is associated with a spike in the percent of angiogenic and apoptotic ECs before eventually returning to 95% quiescent steady state at Day 6. (B) Combination treatment with nintedanib and YAP/TAZ prevents nintedanib associated loss of 95% pericyte quiescent steady state and PMT at 10 kPa. (C) At 20 kPa, combination treatment with nintedanib and a YAP/TAZ inhibitor causes an initial drop in EC quiescence that is recovered to a 95% quiescent steady state at Day 1. (D) Combination treatment delays the loss of 95% pericyte quiescence to Day 2.5 compared to the nintedanib treated alone. However, this is associated with a large influx of PMT. (E) Quantification of resulting tissue level phenotype demonstrates that by preserving pericyte quiescence in 10 kPa, the loss of vessel area due to nintedanib treatment has been recovered. Statistics: N = 5, shading represents 95% confidence interval, bar graph: two-tailed t-test.

Article Snippet: PEGylation of peptides and growth factors PEG hydrogels were functionalized with the following peptides and proteins purchased from Genscript (Piscataway, NJ): RGDS, a fibronectin-derived adhesion ligand, GGGPQGIWGQGK (PQ), a protease-sensitive degradable linker, basic fibroblast growth factor (FGF-2), an angiogenic endothelial cell mitogen, and platelet-derived growth factor (PDGF) which also contributes to angiogenic signaling in ECs and pericytes.

Techniques: Preserving, Two Tailed Test

Journal: bioRxiv

Article Title: Multiscale computational model predicts how environmental changes and drug treatments affect microvascular remodeling in fibrotic disease

doi: 10.1101/2024.03.15.585249

Figure Lengend Snippet: At the initiation of a model the background configuration is set up from an IF image and the initial level of each growth factor is set according to user input. Agents are then placed in specific locations based on IF image data. Then at every time step EC agents will first intake their surrounding environmental cues, input them into Python, and receive a cell fate decision that will then be executed in the ABM. Finally, pericytes repeat the same process as ECs: update cues, solve the ODE in python, then execute the returned cell fate decision. This cycle repeats until the model is terminated.

Article Snippet: PEGylation of peptides and growth factors PEG hydrogels were functionalized with the following peptides and proteins purchased from Genscript (Piscataway, NJ): RGDS, a fibronectin-derived adhesion ligand, GGGPQGIWGQGK (PQ), a protease-sensitive degradable linker, basic fibroblast growth factor (FGF-2), an angiogenic endothelial cell mitogen, and platelet-derived growth factor (PDGF) which also contributes to angiogenic signaling in ECs and pericytes.

Techniques: