Theranostics 2019; 9(5):1232-1246. doi:10.7150/thno.25735

Research Paper

Quantification of human neuromuscular function through optogenetics

Olaia F. Vila1, Sebastien G.M. Uzel2,3, Stephen P. Ma1, Damian Williams4, Joseph Pak1, Roger D. Kamm2, Gordana Vunjak-Novakovic1✉

1. Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA
2. Department of Mechanical Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge MA, USA
3. School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138
4. Columbia University Stem Cell Core Facility, Department of Rehabilitation and Regenerative Medicine, Columbia University, New York, NY 10032, USA

Abstract

The study of human neuromuscular diseases has traditionally been performed in animal models, due to the difficulty of performing studies in human subjects. Despite the unquestioned value of animal models, inter-species differences hamper the translation of these findings to clinical trials. Tissue-engineered models of the neuromuscular junction (NMJ) allow for the recapitulation of the human physiology in tightly controlled in vitro settings.

Methods: Here we report the first human patient-specific tissue-engineered model of the neuromuscular junction (NMJ) that combines stem cell technology with tissue engineering, optogenetics, microfabrication and image processing. The combination of custom-made hardware and software allows for repeated, quantitative measurements of NMJ function in a user-independent manner.

Results: We demonstrate the utility of this model for basic and translational research by characterizing in real time the functional changes during physiological and pathological processes.

Principal Conclusions: This system holds great potential for the study of neuromuscular diseases and drug screening, allowing for the extraction of quantitative functional data from a human, patient-specific system.

Keywords: Tissue Engineering, Induced Pluripotent Stem Cells, Neuromuscular Junctions, Myasthenia Gravis

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How to cite this article:
Vila OF, Uzel SGM, Ma SP, Williams D, Pak J, Kamm RD, Vunjak-Novakovic G. Quantification of human neuromuscular function through optogenetics. Theranostics 2019; 9(5):1232-1246. doi:10.7150/thno.25735. Available from http://www.thno.org/v09p1232.htm