{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T14:03:34Z","timestamp":1784642614446,"version":"3.55.0"},"reference-count":49,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research of the University\u2014Fondazione di Modena","award":["FAR-FOMO 2023"],"award-info":[{"award-number":["FAR-FOMO 2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteosarcopenia is a widespread geriatric condition resulting from the coexistence of osteoporosis and sarcopenia, where the connection between bone and muscle is, in part, driven by bone\u2013muscle crosstalk. Given the close, reciprocal influence of muscle on nerve, and vice versa, it is not surprising that there are corresponding aging changes in the biochemistry and morphology of the neuromuscular junction (NMJ). Indeed, degeneration of motor neurons and progressive disruption of the neuromuscular connectivity were observed in old age. Extracellular vesicles (EVs) derived from human amniotic fluid stem cells (hAFSC), exhibiting antioxidant properties, which can also explain their anti-aging and cytoprotective effects, can be considered as potential treatment for age-related diseases. To study cell interactions under both healthy and pathological conditions occurring in musculo\u2013skeletal apparatus, we developed a three-culture system exploiting the use of well-known transwell supports. This system allows both myotubes and neurons, eventually treated with EVs, and osteoblasts, induced to osteoporosis, to interact physically and biochemically. Collectively, this method allowed us to understand how the modifications induced in osteoblasts during bone disorders trigger a cascade of detrimental effects in the muscle and neuron parts. Moreover, we demonstrated the efficacy of hAFSC-EVs in preventing NMJ dysfunction, muscle atrophy, and osteoblast impairment.<\/jats:p>","DOI":"10.3390\/ijms26167875","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T08:39:07Z","timestamp":1755247147000},"page":"7875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mesenchymal Stromal Cell-Derived Extracellular Vesicles as a Therapeutic Treatment for Osteosarcopenia: Crosstalk Among Neurons, Muscle, and Bone"],"prefix":"10.3390","volume":"26","author":[{"given":"Martina","family":"Gatti","sequence":"first","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"},{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Science, University of Bologna, 40126 Bologna, Italy"}],"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, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3997-6433","authenticated-orcid":false,"given":"Marta","family":"Malenchini","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41124 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, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2393-6804","authenticated-orcid":false,"given":"Eleonora","family":"Ceneri","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Science, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde Y.","family":"Follo","sequence":"additional","affiliation":[{"name":"Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Science, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tullia","family":"Maraldi","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Greco, E.A., Pietschmann, P., and Migliaccio, S. 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