Scleroderma

Autoimmune diseases that precipitate changes to the skin, blood vessels, muscles, and internal organs are collectively known as Scleroderma, and its underlying mechanism consists of abnormal connective tissue growth as a result of a body’s immune system improperly attacking its own healthy tissues.  Symptoms include thickened and/or stiff skin, lethargy, and deficient blood flow to the extremities, particularly during cold exposure.  While the entire cause of Scleroderma remains a mystery, risk factors include family history, certain genetic factors, and exposure to silica.  There is currently no established cure for Scleroderma, and treatments are available, though their efficacy remains incomplete.  Therefore, increased research into novel therapies for this disease is warranted. Biomodels has established a chronic scleroderma model of the disease, as described below.  

Chronic Sclerodermatous Model

Recipient C57Bl/6 mice are pre-conditioned with high dose of total body irradiation prior to the adoptive transfer of bone marrow supplemented with splenocytes harvested from an MHC-mismatched donor mouse (LP/J). Following irradiation and transplant, the recipient mice show transient mild weight loss followed by recovery up to approximately day 21 to 28, after which they develop a progressively worsening disease characterized by weight loss, increasing GVHD score, and development of sclerodermatous skin lesions. Animals are monitored up to day 60; endpoint survival in untreated mice is approximately 50%.

Study Design Table

Model Description Duration Endpoints
Allogeneic Bone Marrow Transplant GVHD reaction is assessed using a modified 5-criteria score. Initial recovery from conditioning regimen is followed by progressive exacerbation of disease from day 21-28 onwards 9-10 Weeks GVHD score, Weight, Survival, Histology

 

Timeline schematic showing induction schedule and expected onset of disease. Daily measurements include weight change and GVHD score; endpoint collections include blood, broncho-alveolar lavage, and histopathological analysis of selected tissues (e.g. skin, lungs).
Representative photographs showing the development of sclerodermatous skin lesions over time. Animals are briefly anaesthetized with isoflurane during photography; the animal shown here was photographed immediately after sacrifice on day 45.
Subscribe to RSS - Scleroderma