Development of humanized 3D skin models for Systemic sclerosis (SSc)
Systemic sclerosis (SSc) is a chronic systemic autoimmune disease characterized by vasculopathy, inflammation and fibrosis. Skin fibrosis is the major cause of impairment in these patients. Systemic sclerosis is a rare disease; it also has a high morbidity and mortality. Intensive research in the last years improved our understanding of the disease. This allows earlier diagnosis and a better management of the disease and treatments for specific complications. However, there are currently no established specific therapies for SSc. Therefore, there is a high-unmet need for novel anti-fibrotic therapies for SSc. Current in vivo pathophysiological studies using animal models are cost-intensive and do not reflect aspects of the human disease due to different physiology and genetics. In vitro studies mainly relay on cell monolayers. They do not consider the spatial organization of a cell within the 3-dimensional architecture of organs and the interactions of cells and the environment resulting in a poor predictable power of pre-clinical cell-based drug screening assays. 3D culture systems are more physiologically relevant since they mimic the in vivo situation and useful tools to study pathophysiology of a disease and for proof of concept studies. Our aim is to engineer 3D skin equivalents with primary skin fibroblasts and keratinocytes from patients with SSc and healthy controls and to transplant these 3D skin equivalents onto immuno-incompetent mice to create a humanized mouse model of SSc.
Astrid Jüngel, Oliver Distler