Cooper2015 - Modeling the effects of systemic mediators on the inflammatory phase of wound healing

  public model
Model Identifier
BIOMD0000000855
Short description 
This is an ordinary differential equation-based mathematical model describing the inflammatory phase of the wound healing response. The model describes the interactions in the wound between wound debris, pathogens, neutrophils and macrophages, as well as the modulation of these interactions by estrogen and cortisol.
Format
SBML (L2V4)
Related Publication
  • Modeling the effects of systemic mediators on the inflammatory phase of wound healing.
  • Cooper RL, Segal RA, Diegelmann RF, Reynolds AM
  • Journal of theoretical biology , 2/ 2015 , Volume 367 , pages: 86-99 , PubMed ID: 25446708
  • Department of Mathematics and Applied Mathematics, Virginia Commonwealth University, Richmond, VA 23284-2014, USA; The VCU Johnson Center, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0614, USA.
  • The normal wound healing response is characterized by a progression from clot formation, to an inflammatory phase, to a repair phase, and finally, to remodeling. In many chronic wounds there is an extended inflammatory phase that stops this progression. In order to understand the inflammatory phase in more detail, we developed an ordinary differential equation model that accounts for two systemic mediators that are known to modulate this phase, estrogen (a protective hormone during wound healing) and cortisol (a hormone elevated after trauma that slows healing). This model describes the interactions in the wound between wound debris, pathogens, neutrophils and macrophages and the modulation of these interactions by estrogen and cortisol. A collection of parameter sets, which qualitatively match published data on the dynamics of wound healing, was chosen using Latin Hypercube Sampling. This collection of parameter sets represents normal healing in the population as a whole better than one single parameter set. Including the effects of estrogen and cortisol is a necessary step to creating a patient specific model that accounts for gender and trauma. Utilization of math modeling techniques to better understand the wound healing inflammatory phase could lead to new therapeutic strategies for the treatment of chronic wounds. This inflammatory phase model will later become the inflammatory subsystem of our full wound healing model, which includes fibroblast activity, collagen accumulation and remodeling.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Rahuman Sheriff
Modellers: Rahuman Sheriff, Johannes Meyer

Metadata information

is (2 statements)
BioModels Database MODEL1911130002
BioModels Database BIOMD0000000855

isDescribedBy (1 statement)
PubMed 25446708

isDerivedFrom (3 statements)
PubMed 22810171
PubMed 16584750
PubMed 16616206

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (5 statements)
Mathematical Modelling Ontology Ordinary differential equation model
ChEBI estrogen
ChEBI cortisol
Cell Type Ontology macrophage
Cell Type Ontology neutrophil

Curation status
Curated
Tags

Connected external resources

Name Description Size Actions

Model files
Cooper2015.xml SBML L2V4 Representation of Cooper2015 - Modeling the effects of systemic mediators on the inflammatory phase of wound healing 78.95 KB Preview | Download

Additional files
Cooper2015.cps COPASI file of Cooper2015 - Modeling the effects of systemic mediators on the inflammatory phase of wound healing 119.75 KB Preview | Download
Cooper2015.sedml SED-ML file of Cooper2015 - Modeling the effects of systemic mediators on the inflammatory phase of wound healing 2.68 KB Preview | Download

  • Model originally submitted by : Johannes Meyer
  • Submitted: Nov 13, 2019 1:58:34 PM
  • Last Modified: Oct 5, 2021 8:02:21 PM
Revisions
  • Version: 4 public model Download this version
    • Submitted on: Oct 5, 2021 8:02:21 PM
    • Submitted by: Rahuman Sheriff
    • With comment: Automatically added model identifier BIOMD0000000855
  • Version: 2 public model Download this version
    • Submitted on: Nov 13, 2019 1:58:34 PM
    • Submitted by: Johannes Meyer
    • With comment: Automatically added model identifier BIOMD0000000855

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
P

C80324 		0.1 item
Pt

C120869 		2.0 item
M

macrophage 		0.0 item
N

CL:0000775 		0.1 item
Reactions
Reactions Rate Parameters
P => ; N compartment*kpn*P*N*(1+ken*E) kpn = 35.03; ken = 5.37; E = 0.0
Pt => ; N compartment*kptn*Pt*N*(1+ken*N) ken = 5.37; kptn = 2.03
Pt => compartment*mupt*Pt mupt = 0.37
=> M compartment*smr*R1/(mumr+R1) smr = 0.17; mumr = 0.54; R1 = 85.91
P => compartment*kpm*P*fi2*(1+kem*E) fi2 = 0.0; kem = 4.97; E = 0.0; kpm = 34.8
N => Pt compartment*mun*N mun = 1.02
M => compartment*mum*M mum = 0.5
=> N compartment*fEN fEN = 0.265979268957992
Curator's comment:
(added: 13 Nov 2019, 13:58:26, updated: 13 Nov 2019, 13:58:26)
Reproduced plots of Figure 10 in the original publication. From top to bottom the variables plotted are debris, neutrophils, and macrophages. Model simulated and plots produced using COPASI 4.24 (Build 197).