A Functional 3D Bioprinted Neuromuscular Junction Model for Therapeutic Development of Myopathies and Neuromuscular Diseases

Authors

• SA Frebert
• CA Antich
• S Kundu
• P Ormanoglu
• J Colon
• Y Zou
• Mj Song
• M Ward
• C Bonnemann
• M Ferrer

Abstract

Myopathies and neuromuscular illnesses encompass several conditions that lead to a progressive decline in motor function due to faulty motoneurons (MN), muscle tissue, or a mix of both. Although there are several treatments to relieve symptoms, a cure has not yet been found. Our lab has developed an innovative platform that enables rapid and high-throughput biofabrication of human muscle tissue equivalents for therapeutics screening and discovery. The 3D muscle tissue assay system consists of a bioprinted muscle structure composed of human iPSCs-derived myoblasts and fibroblasts embedded in a hydrogel casted to a pillar-based multi-well culture plate to enable the functional measurement of muscle contractility. Our work is focused on recreating various disorders included in Congenital Myasthenic Syndromes (CMS) to evaluate the efficacy of novel therapeutic gene therapies being developed by NCATS and NINDS, as part of PaVe-GT program. Our results showed that we were able to replicate the clinical features of both deficiencies in the biofabricated muscle tissues. This was evidenced by impaired contractility, with a significant drop in contractile force and noticeable fatigue after chemical (acetylcholine) and electrical stimulation, respectively. Currently, we are testing the safety and effectiveness of gene therapy using adeno-associated virus (AAV) delivery. This new 3D functional muscle tissue platform has potential to improve understanding of muscle and neuromuscular pathologies, while also providing a predictive tool for new therapeutic approaches.

Scientific Focus Area: Biomedical Engineering and Biophysics

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