BioMAP® Fibrosis Panels

    The BioMAP Fibrosis Panel models fibrotic diseases, wound healing and extracellular matrix remodeling under inflammatory and pro-fibrotic conditions.   The systems in this panel are comprised of human primary fibroblasts cultured alone or co-cultured with either primary renal or small airway epithelial cells to allow the measurement of drug or test agent effects on protein biomarkers.  The biomarker activity profiles can be compared to the profiles of selected clinical drugs and reference compounds from BioMAP database to gain insights into mechanism of action, efficacy and safety-related effects of test agents.

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Drug Discovery Applications

  • Investigation of effects of the test agent on fibrosis, wound healing, matrix remodeling and kidney and lung biology
  • Biological mechanism of action, efficacy and safety
  • Biomarker discovery
  • Benchmarking to clinical drugs and reference compounds

Fibrosis Panel Advantages

  • Select benchmark compounds exhibited differential modulation of readouts across MyoF, REMyoF and SAEMyoF systems, indicating the key influence of the tissue-specific epithelia on the fibrotic disease biology
  • Common protein biomarker readouts across REMyoF and SAEMyoF systems enable comparison of effects on organ-specific fibrosis and inflammation models
  • Screening in one or more Fibrosis systems could be used to differentiate compounds and help guide indication selection
 
Fibrosis Panel

Service

  • Test agent (chemical compound or biologic) profiling in selected BioMAP Systems
  • 4 concentrations in triplicate

Description

  • Annotation Identification and biological interpretation of relevant BioMAP biomarker activities (readouts)
  • Benchmarking Direct comparison of test agent to a specified clinical drug or reference compound from BioMAP database (list available upon request)

Deliverables

  • Study Report BioMAP profile plots, annotation of activities with respect to biological significance, graphical overlays of test agent and drug or reference compound profiles, expert data interpretation and analysis
  • Data Report Log ratio data tables, table of cytotoxicities, table of active biomarker readouts
 

Schematic of Mechanism of Fibrosis and Wound Healing Modeled in BioMAP Fibrosis Systems

 
 
Biological and Disease Relevance Biomarker Readouts

Myofibroblast activation

Alpha smooth muscle actin (α-SMA), E-cadherin, N-cadherin

Fibrosis related matrix activities

Collagen-I, Collagen-III, Collagen-IV, Decorin, MMP-1, MMP-9, TIMP-1, PAI-1

Tissue remodeling/wound healing activities 

EGFR, Keratin 8/18, tPA, uPA, bFGF, soluble VEGF

Inflammation-related activities

soluble IL-6, IL-8, soluble IL-8, IP-10, I-TAC, VCAM-1, M-CSF

Fibrosis Systems & Biomarker Readouts

System ▲RelevanceCell TypeBiomarker Readout
MyoFChronic Inflammation, Fibrosis, Matrix Remodeling, Wound HealingLung fibroblastsbFGF, CD106/VCAM-1, Collagen I, Collagen III, Collagen IV, CXCL8/IL-8, Decorin, MMP-1, PAI-I, SRB, TIMP-1, α-SM Actin
REMyoFChronic Inflammation, Matrix Remodeling, Renal Fibrosis, Wound HealingLung fibroblasts + Renal proximal tubule epithelial cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, E-Cadherin, EGFR, Keratin 8/18, M-CSF, MMP-1, MMP-9, N-Cadherin, PAI-I, sIL-6, sIL-8, SRB, sVEGF, TIMP-1, tPA, uPA, α-SM Actin
SAEMyoFChronic Inflammation, Matrix Remodeling, Pulmonary Fibrosis, Wound HealingLung fibroblasts + Small airway epithelial cellsCCL2/MCP-1, CD106/VCAM-1, Collagen I, Collagen III, CXCL10/IP-10, CXCL11/I-TAC, E-Cadherin, EGFR, M-CSF, MMP-1, MMP-9, N-Cadherin, PAI-I, sIL-6, sIL-8, SRB, sVEGF, TIMP-1, uPA, α-SM Actin