Systemic Sclerosis

Systemic sclerosis is a complex multisystem autoimmune disease characterized by inflammation, vascular pathology, and widespread fibrosis that affects multiple organ systems. Two hallmarks of the disease include skin fibrosis and interstitial lung disease which includes idiopathic pulmonary fibrosis. Currently, there is no cure for this disease and drug development has been hampered by limited pre-clinical animal models.

Subcutaneous Osmotic Pump administered Bleomycin-Induced Systemic Sclerosis

Subcutaneously administered bleomycin induces dermal and pulmonary fibrosis over the course of 28 days in this model. After being anesthetized, animals have an osmotic pump containing bleomycin implanted subcutaneously in the back. Animals are evaluated daily for body weight and respiratory status. After animals are sacrificed, collagen thickness and content, fibrosis scores, and other markers of skin fibrosis are determined as well as collagen content and fibrosis scores in the lung.

Study Design Table

Model Description Duration Endpoints
Subcutaneous Osmotic Pump Bleomycin-induced systemic sclerosis Bleomycin slowly released subcutaneously for a period of up to 28 days 28 Days Body weight, Lung weight, Respiratory Status, Collagen thickness and content of the skin, Histological analysis of skin, collagen content and fibrosis score of lungs, lung mechanics measurements
 
Dose dependent increases in dermal fibrosis are observed histologically after subcutaneous osmotic pump-delivered bleomycin exposure
Dermal thickness and fibrosis scores resulting from subcutaneous osmotic pump-delivered bleomycin exposure
Dose dependent increases in fibrosis are observed histologically after subcutaneous osmotic pump-delivered bleomycin exposure
 Pulmonary fibrosis scores resulting from subcutaneous osmotic pump-delivered bleomycin exposure
Decreased body weight and increased lung weight are associated with increases in subcutaneous osmotic pump-delivered bleomycin exposure
Increased inflammatory cells are found in bronchoalveolar lavage fluid of animals exposed to subcutaneous osmotic pump-delivered bleomycin
Decreased lung function is associated with exposure to subcutaneous osmotic pump-delivered bleomycin
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