In Silico Translation of Cellular and Molecular Mechanisms to Clinical Phenomena in Atheroma Development with an Agent Based Model

Regenerative medicine involves methods to control and modify normal tissue repair processes. Polymer and cell constructs are under research to create tissue that replaces the affected area in cardiac tissue after myocardial infarction (MI). The aim of the present study is to evaluate the behavior of differentiated and undifferentiated mesenchymal stem cells (MSCs) in vitro and in silico and to compare the results that both offer when it comes to the design process of biodevices for the treatment of infarcted myocardium in biomodels. To assess in vitro behavior, MSCs are isolated from rat bone marrow and seeded undifferentiated and differentiated in multiple scaffolds of a gelled biomaterial. Subsequently, cell behavior is evaluated by trypan blue and fluorescence microscopy, which showed that the cells presented high viability and low cell migration in the biomaterial. An agent-based model intended to reproduce as closely as possible the behavior of individual MSCs by simulating cellular-level processes was developed, where the in vitro results are used to identify parameters in the agent-based model that is developed, and which simulates cellular-level processes: Apoptosis, differentiation, proliferation, and migration. Thanks to the results obtained, suggestions for good results in the design and fabrication of the proposed scaffolds and how an agent-based model can be helpful for testing hypothesis are presented in the discussion. It is concluded that assessment of cell behavior through the observation of viability, proliferation, migration, inflammation reduction, and spatial composition in vitro and in silico, represents an appropriate strategy for scaffold engineering.

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Hybrid agent-based model for quantitative in-silico cell-free protein synthesis

Biosystems ◽

10.1016/j.biosystems.2016.07.008 ◽

2016 ◽

Vol 150 ◽

pp. 22-34 ◽

Cited By ~ 3

Author(s):

Anton Semenchenko ◽

Guilherme Oliveira ◽

A.P.F. Atman

Keyword(s):

Protein Synthesis ◽

In Silico ◽

Agent Based Model ◽

Agent Based ◽

Free Protein ◽

Hybrid Agent ◽

Cell Free Protein Synthesis

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An In Silico Agent-Based Model Demonstrates Reelin Function in Directing Lamination of Neurons during Cortical Development

PLoS ONE ◽

10.1371/journal.pone.0110415 ◽

2014 ◽

Vol 9 (10) ◽

pp. e110415 ◽

Cited By ~ 7

Author(s):

James R. Caffrey ◽

Barry D. Hughes ◽

Joanne M. Britto ◽

Kerry A. Landman

Keyword(s):

In Silico ◽

Cortical Development ◽

Agent Based Model ◽

Agent Based

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In Silico Modeling of Biofilm Formation by Nontypeable Haemophilus influenzae In Vivo

mSphere ◽

10.1128/msphere.00254-19 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 4

Author(s):

Jonathan R. Brown ◽

Joseph Jurcisek ◽

Vinal Lakhani ◽

Ali Snedden ◽

William C. Ray ◽

...

Keyword(s):

Haemophilus Influenzae ◽

In Silico ◽

Biofilm Formation ◽

Host Responses ◽

Model Parameters ◽

Agent Based Model ◽

Content Type ◽

Agent Based

ABSTRACT Biofilms formed by nontypeable Haemophilus influenzae (NTHI) bacteria play an important role in multiple respiratory tract diseases. Visual inspection of the morphology of biofilms formed during chronic infections shows distinct differences from biofilms formed in vitro. To better understand these differences, we analyzed images of NTHI biofilms formed in the middle ears of Chinchilla lanigera and developed an in silico agent-based model of the formation of NTHI biofilms in vivo. We found that, as in vitro, NTHI bacteria are organized in self-similar patterns; however, the sizes of NTHI clusters in vivo are more than 10-fold smaller than their in vitro counterparts. The agent-based model reproduced these patterns and suggested that smaller clusters occur due to elimination of planktonic NTHI cells by the host responses. Estimation of model parameters by fitting simulation results to imaging data showed that the effects of several processes in the model change during the course of the infection. IMPORTANCE Multiple respiratory illnesses are associated with formation of biofilms within the human airway by NTHI. However, a substantial amount of our understanding of the mechanisms that underlie NTHI biofilm formation is obtained from in vitro studies. Our in silico model that describes biofilm formation by NTHI within the middle ears of Chinchilla lanigera will help isolate processes potentially responsible for the differences between the morphologies of biofilms formed in vivo versus those formed in vitro. Thus, the in silico model can be used to glean mechanisms that underlie biofilm formation in vivo and connect those mechanisms to those obtained from in vitro experiments. The in silico model developed here can be extended to investigate potential roles of specific host responses (e.g., mucociliary clearance) on NTHI biofilm formation in vivo. The developed computational tools can also be used to analyze and describe biofilm formation by other bacterial species in vivo.

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