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- Customized Solutions for Bronchiolitis Obliterans Syndrome Drug Discovery and Development
Customized Solutions for Bronchiolitis Obliterans Syndrome Drug Discovery and Development
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Bronchiolitis obliterans syndrome (BOS) is a progressive fibrotic lung disease marked by the irreversible obstruction of small airways and most commonly develops as a complication of lung transplantation or chemical exposure. Therapeutics are few, and pathophysiology complex, advancing research demands highly specialized and reliable preclinical models.
Protheragen is an end-to-end, custom preclinical research services provider, supporting the development of novel diagnostics and therapeutics for BOS by combining sound scientific research with deep domain expertise.
Integrated Preclinical Services for Bronchiolitis Obliterans Syndrome (BOS)
Biomarker Development Services
Identification and validation of molecular, cellular, or imaging biomarkers for early detection, disease stratification, and therapy monitoring.
- Biomarker Discovery and Identification
- Biomarker Assay Development and Validation
- Biomarker Quantitative and Qualitative Analysis
Custom assays utilizing primary human cells or relevant cell lines to model airway injury, inflammation, and fibrosis in controlled environments.
- Cell-based Profiling
- High-Sensitivity Biochemical Assays
- Gene Expression Analysis
- Biophysical Interaction Analysis
Establishment and characterization of relevant animal models that recapitulate key features of BOS progression.
- Allograft Transplantation Models
- Syngeneic Orthotopic Graft Models
- Chemically-Induced Models
Pharmacokinetic Study Services
Comprehensive ADME (Absorption, Distribution, Metabolism, Excretion) profiling to understand the behavior of candidate therapeutics.
- Acute Toxicity Studies
- Chronic Toxicity Evaluation
- Organ-Specific Toxicity Assessment
- Systemic Toxicity Studies
- Special Toxicology Studies
Case Study 01-Diacetyl (DA)-Induced In Vitro BOS Model Development
An in vitro system of bronchiolitis obliterans was investigated by cultivating human primary bronchial epithelial cells (HPBECs) at the air-liquid interface (ALI). To simulate injury leading to obliterative pathology, cultures were treated with diacetyl (DA) vapor for 1 h on days 0, 2, and 4. This ALI-derived model successfully replicated major disease parameters, such as epithelial injury and impaired barrier function. On day 6, therapeutic intervention was carried out, giving a test compound at the end concentration of 5 µM.
Fig.1 Schematic of the DA-induced in vitro BOS model.
Analysis revealed that DA exposure strongly elevated fibrotic markers (α-SMA, fibronectin, and vimentin) and pro-inflammatory cytokines (IL-1β, TNF-α), whereas E-cadherin, an epithelial biomarker, was downregulated, consistent with fibrotic activation and epithelial integrity loss. Therapeutic intervention reversed these alterations, rescued E-cadherin expression, inhibited fibrotic and mesenchymal markers, and suppressed cytokine release, thereby confirming the model's relevance and the compound's potential.
Fig.2 Characterization of the BOS model and drug efficacy evaluation. (A-B) ELISA quantification of IL-1β and TNF-α in supernatants. (C-D) Immunofluorescence assessment of E-cadherin and vimentin expression. Data are presented as mean ± SEM (n=5; *p < 0.05).
Case Study 02-Heterotopic Tracheal Transplantation (HTT) Model Development
The developed model of HTT reliably elicited luminal fibrosis and progressive airway obliteration, thus recapitulating several key aspects of obliterative bronchiolitis as well as offering an in vivo system to test potential therapeutics. To assess efficacy, a comparative study was conducted to compare with mice treated with a neutralizing antibody of known specificity or a control immunoglobulin.
Fig.3 Experimental timeline and design of the antibody therapy study.
Histological and immunohistochemical examination on day 21 indicated that the model was set up successfully, and therapy effects were evident. Therapy with an antibody drastically decreased the luminal obstruction ratio and the area of α-SMA (a marker of activated myofibroblasts) positive region, indicating strong antifibrotic activity.
Fig.4 Evaluation of airway occlusion and anti-fibrotic efficacy following antibody therapy. (A) Luminal obstruction ratio. (B-C) α-SMA-positive area in the lumen and the submucosa. Data are presented as mean ± SEM (n=5; ***p < 0.001, *p < 0.05).
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Protheragen, blending scientific depth with operational excellence, brings reliable data-driven insights to de-risk and propel your BOS-focused projects. All services are customized to the research goals of investigators, ensuring relevance and translational value. To see how our specific expertise and services can assist your program, please contact with our team to initiate a consultation.
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All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.