Journal
BIOMATERIALS
Volume 225, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2019.119537
Keywords
Microfluidics; poly(ethylene-alt-maleic anhydride); Neuromuscular circuit; Skeletal muscle; Rabies viral tracing; Motor unit
Funding
- Deutsche Forschungsgemeinschaft (DFG)
- CRTD, Technische Universitat Dresden
- DFG Research Center (DFG) [FZT 111]
- Cluster of Excellence (DFG) [EXC 168]
- Hans und Ilse Breuer Stiftung
- European Union [643417]
- Bundesministerium fur Bildung und Forschung [01EK1606A, 01ED1601B]
- Germany, Bundesministerium fur Bildung and Forschung
- Israel, Ministry of Health
- Italy, Ministero dell'Istruzione dell'Universita e della Ricerca
- Sweden, Swedish Research Council
- Switzerland, Swiss National Science Foundation
Ask authors/readers for more resources
Neuromuscular circuits (NMCs) are vital for voluntary movement, and effective models of NMCs are needed to understand the pathogenesis of, as well as to identify effective treatments for, multiple diseases, including Duchenne's muscular dystrophy and amyotrophic lateral sclerosis. Microfluidics are ideal for recapitulating the central and peripheral compartments of NMCs, but myotubes often detach before functional NMCs are formed. In addition, microfluidic systems are often limited to a single experimental unit, which significantly limits their application in disease modeling and drug discovery. Here, we developed a microfluidic platform (MFP) containing over 100 experimental units, making it suitable for medium-throughput applications. To overcome detachment, we incorporated a reactive polymer surface allowing customization of the environment to culture different cell types. Using this approach, we identified conditions that enable long-term co-culture of human motor neurons and myotubes differentiated from human induced pluripotent stem cells inside our MFP. Optogenetics demonstrated the formation of functional NMCs. Furthermore, we developed a novel application of the rabies tracing assay to efficiently identify NMCs in our MFP. Therefore, our MFP enables large-scale generation and quantification of functional NMCs for disease modeling and pharmacological drug targeting.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available