The Neuromuscular Junction (NMJ) is a chemical synapse localized between the terminal branches of the spinal motor neurons and myofibers. In the past two decades coculture systems to generate the NMJ in culture are developed to address concerns about animal models, despite the complexity of its highly specialized structure makes the in vitro modeling a challenging task. Microfluidics, unlike mass cocultures, allow spatial and temporal control over different microenvironment by manipulating either neural cells or muscle cell populations independently. Therefore, exploiting an organ-on-a-chip approach, the aim is to obtain a reliable and predictive in vitro human model of NMJ in physiological and pathological conditions, to investigate the occurrence of synapse detriment in alpha-sarcoglycanopathy, a subtype of limb-girdle muscular dystrophy. For this purpose, motor neurons derived from human induced pluripotent stem cells (hiPSCs) and either healthy or alpha-sarcoglycan mutant human myogenic progenitors are seeded in two separated chambers of a microfluidic device. Differentiated myotubes and hiPSCs-derived motor neurons on-chip are able to establish points of interaction where pre- and postsynaptic structures colocalize. Moreover, the attraction of motor neurons axons by muscle fibers and the NMJ maturation appear to be affected by the muscular compartment, being impaired by the dystrophic cellular component.

Dystrophic Muscle Affects Motoneuron Axon Outgrowth and NMJ Assembly / Fornetti, Ersilia; Testa, Stefano; DE PAOLIS, Francesca; Fuoco, Claudia; Bernardini, Sergio; Pozo Devoto, Victorio; Bernard Stokin, Gorazd; Maria Giannitelli, Sara; Rainer, Alberto; Bigot, Anne; Zoccali, Carmine; Baldi, Jacopo; Sandon??, Doriana; Rizzi, Roberto; Bearzi, Claudia; Forte, Giancarlo; Cannata, Stefano; Gargioli, Cesare. - In: ADVANCED MATERIALS TECHNOLOGIES. - ISSN 2365-709X. - 7:7(2022), p. 2101216. [10.1002/admt.202101216]

Dystrophic Muscle Affects Motoneuron Axon Outgrowth and NMJ Assembly

Francesca De Paolis;Carmine Zoccali;Roberto Rizzi;Cesare Gargioli
2022

Abstract

The Neuromuscular Junction (NMJ) is a chemical synapse localized between the terminal branches of the spinal motor neurons and myofibers. In the past two decades coculture systems to generate the NMJ in culture are developed to address concerns about animal models, despite the complexity of its highly specialized structure makes the in vitro modeling a challenging task. Microfluidics, unlike mass cocultures, allow spatial and temporal control over different microenvironment by manipulating either neural cells or muscle cell populations independently. Therefore, exploiting an organ-on-a-chip approach, the aim is to obtain a reliable and predictive in vitro human model of NMJ in physiological and pathological conditions, to investigate the occurrence of synapse detriment in alpha-sarcoglycanopathy, a subtype of limb-girdle muscular dystrophy. For this purpose, motor neurons derived from human induced pluripotent stem cells (hiPSCs) and either healthy or alpha-sarcoglycan mutant human myogenic progenitors are seeded in two separated chambers of a microfluidic device. Differentiated myotubes and hiPSCs-derived motor neurons on-chip are able to establish points of interaction where pre- and postsynaptic structures colocalize. Moreover, the attraction of motor neurons axons by muscle fibers and the NMJ maturation appear to be affected by the muscular compartment, being impaired by the dystrophic cellular component.
2022
microfluidic; muscle dystrophy; neural muscular junction; NMJ modeling; organ on a chip
01 Pubblicazione su rivista::01a Articolo in rivista
Dystrophic Muscle Affects Motoneuron Axon Outgrowth and NMJ Assembly / Fornetti, Ersilia; Testa, Stefano; DE PAOLIS, Francesca; Fuoco, Claudia; Bernardini, Sergio; Pozo Devoto, Victorio; Bernard Stokin, Gorazd; Maria Giannitelli, Sara; Rainer, Alberto; Bigot, Anne; Zoccali, Carmine; Baldi, Jacopo; Sandon??, Doriana; Rizzi, Roberto; Bearzi, Claudia; Forte, Giancarlo; Cannata, Stefano; Gargioli, Cesare. - In: ADVANCED MATERIALS TECHNOLOGIES. - ISSN 2365-709X. - 7:7(2022), p. 2101216. [10.1002/admt.202101216]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1676412
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