Abstract：
: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.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Bellmann J,Goswami RY,Girardo S,Rein N,Hosseinzadeh Z,Hicks MR,Busskamp V,Pyle AD,Werner C,Sterneckert Jdoi
10.1016/j.biomaterials.2019.119537subject
Has Abstractpub_date
2019-12-01 00:00:00pages
119537eissn
0142-9612issn
1878-5905pii
S0142-9612(19)30636-2journal_volume
225pub_type
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