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Open AccessArticle

Neuromuscular Activity Induces Paracrine Signaling and Triggers Axonal Regrowth after Injury in Microfluidic Lab-On-Chip Devices

1
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain
2
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain
3
Department of Cell Biology, Physiology and Immunology, Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Spain
4
Institute of Neuroscience, University of Barcelona, 08028 Barcelona, Spain
5
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBERBBN), 28029 Madrid, Spain
6
Department of Electronics and Biomedical Engineering, Universitat de Barcelona, 08028 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(2), 302; https://doi.org/10.3390/cells9020302
Received: 12 December 2019 / Revised: 17 January 2020 / Accepted: 23 January 2020 / Published: 27 January 2020
(This article belongs to the Section Cell Motility and Adhesion)
Peripheral nerve injuries, including motor neuron axonal injury, often lead to functional impairments. Current therapies are mostly limited to surgical intervention after lesion, yet these interventions have limited success in restoring functionality. Current activity-based therapies after axonal injuries are based on trial-error approaches in which the details of the underlying cellular and molecular processes are largely unknown. Here we show the effects of the modulation of both neuronal and muscular activity with optogenetic approaches to assess the regenerative capacity of cultured motor neuron (MN) after lesion in a compartmentalized microfluidic-assisted axotomy device. With increased neuronal activity, we observed an increase in the ratio of regrowing axons after injury in our peripheral-injury model. Moreover, increasing muscular activity induces the liberation of leukemia inhibitory factor and glial cell line-derived neurotrophic factor in a paracrine fashion that in turn triggers axonal regrowth of lesioned MN in our 3D hydrogel cultures. The relevance of our findings as well as the novel approaches used in this study could be useful not only after axotomy events but also in diseases affecting MN survival. View Full-Text
Keywords: neuromuscular junction; microfluidics; axotomy; paracrine signaling neuromuscular junction; microfluidics; axotomy; paracrine signaling
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Sala-Jarque, J.; Mesquida-Veny, F.; Badiola-Mateos, M.; Samitier, J.; Hervera, A.; del Río, J.A. Neuromuscular Activity Induces Paracrine Signaling and Triggers Axonal Regrowth after Injury in Microfluidic Lab-On-Chip Devices. Cells 2020, 9, 302.

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