{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:01:23Z","timestamp":1780372883645,"version":"3.54.1"},"reference-count":63,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T00:00:00Z","timestamp":1677801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Excellence 2018\u20132022"},{"name":"mobility activities for young researchers"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuromuscular junctions (NMJs) are specialized synapses, crucial for the communication between spinal motor neurons (MNs) and skeletal muscle. NMJs become vulnerable in degenerative diseases, such as muscle atrophy, where the crosstalk between the different cell populations fails, and the regenerative ability of the entire tissue is hampered. How skeletal muscle sends retrograde signals to MNs through NMJs represents an intriguing field of research, and the role of oxidative stress and its sources remain poorly understood. Recent works demonstrate the myofiber regeneration potential of stem cells, including amniotic fluid stem cells (AFSC), and secreted extracellular vesicles (EVs) as cell-free therapy. To study NMJ perturbations during muscle atrophy, we generated an MN\/myotube co-culture system through XonaTM microfluidic devices, and muscle atrophy was induced in vitro by Dexamethasone (Dexa). After atrophy induction, we treated muscle and MN compartments with AFSC-derived EVs (AFSC-EVs) to investigate their regenerative and anti-oxidative potential in counteracting NMJ alterations. We found that the presence of EVs reduced morphological and functional in vitro defects induced by Dexa. Interestingly, oxidative stress, occurring in atrophic myotubes and thus involving neurites as well, was prevented by EV treatment. Here, we provided and validated a fluidically isolated system represented by microfluidic devices for studying human MN and myotube interactions in healthy and Dexa-induced atrophic conditions\u2014allowing the isolation of subcellular compartments for region-specific analyses\u2014and demonstrated the efficacy of AFSC-EVs in counteracting NMJ perturbations.<\/jats:p>","DOI":"10.3390\/ijms24054944","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T03:49:08Z","timestamp":1678074548000},"page":"4944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Human Neuromuscular Junction on a Chip: Impact of Amniotic Fluid Stem Cell Extracellular Vesicles on Muscle Atrophy and NMJ Integrity"],"prefix":"10.3390","volume":"24","author":[{"given":"Martina","family":"Gatti","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2776-2892","authenticated-orcid":false,"given":"Katarina Stoklund","family":"Dittlau","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Experimental Neurology and Leuven Brain Institute, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"},{"name":"VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6023-5846","authenticated-orcid":false,"given":"Francesca","family":"Beretti","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1701-9109","authenticated-orcid":false,"given":"Laura","family":"Yedigaryan","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration, Stem Cell and Developmental Biology, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3454-1441","authenticated-orcid":false,"given":"Manuela","family":"Zavatti","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3633-8818","authenticated-orcid":false,"given":"Pietro","family":"Cortelli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40127 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0587-0112","authenticated-orcid":false,"given":"Carla","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-9111","authenticated-orcid":false,"given":"Emma","family":"Bertucci","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Mothers, Children and Adults, Azienda Ospedaliero Universitaria Policlinico, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-4067","authenticated-orcid":false,"given":"Ludo","family":"Van Den Bosch","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Experimental Neurology and Leuven Brain Institute, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"},{"name":"VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2422-3757","authenticated-orcid":false,"given":"Maurilio","family":"Sampaolesi","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration, Stem Cell and Developmental Biology, KU Leuven\u2014University of Leuven, 3000 Leuven, Belgium"},{"name":"Histology and Medical Embryology Unit, Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tullia","family":"Maraldi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic 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