Complex Dimensional in Vitro Human Skin Tissue Models for Scleroderma

Abstract Project Summary Scleroderma Systemic Sclerosis SSc is an autoimmune disease of unknown etiology that is characterized by vascular dysfunction fibrosis and inflammation One in three patients dies within years of diagnosis giving SSc the highest case fatality rate of any systemic autoimmune disease A lack of biologically relevant human SSc disease models has created a critical unmet need for more efficient preclinical drug screening models that can provide faster more cost effective ways of predicting the success or failure of drugs designed to treat SSc Recent advances in tissue engineering have resulted in D skin tissue based disease models that can provide in vitro models of SSc that closely mimic this disease in humans This will shorten the preclinical drug development timeline save animal lives reduce drug failure rates and inform FDA decision making for the development of new and effective disease therapeutics The development of D skin like tissue models that accurately recapitulate the SSc phenotype will be an important advancement over currently available monolayer D tissue cultures Bringing D skin models into Celdara Medical allows us to pair this promising in vitro system with our existing portfolio of SSc diagnostics and SSc fibrosis and cancer drug development efforts Beyond our immediate goals of optimizing and exploiting these well established D skin like tissues models for drug screening will advance complex tissue models for other organ systems such as lung By using multiple patient derived cell types we will optimize D tissues to establish proof of concept that robust SSc specific D tissue models can serve as preclinical drug screening platforms for new therapeutic agents for SSc Our aims are to optimize fabrication of SSc specific D tissue models harboring primary SSc derived fibroblasts macrophages M s and keratinocytes and To analyze the cell biology tissue properties and genomic similarity of D skin like tissues made from SSc cells against SSc patient skin biopsies Project Narrative The goal of this proposal is to fabricate and characterize D bioengineered skin like tissue models that mimic systemic sclerosis SSc using patient derived keratinocytes fibroblasts and macrophages ultimately for preclinical drug testing in a physiologically relevant system Development of robust predictive and cost effective skin models will improve the ability to test and identify the drugs most likely to be effective in SSc patients thereby providing a vast improvement for preclinical drug development