{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T03:13:25Z","timestamp":1785813205769,"version":"3.56.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["732163"],"award-info":[{"award-number":["732163"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JOR Spine"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Intradiscal transplantation of mesenchymal stromal cells (MSCs) has emerged as a promising therapy for intervertebral disc degeneration (IDD). However, the hostile microenvironment of the intervertebral disc (IVD) may compromise the survival of implanted cells. Interestingly, studies reported that paracrine factors, such as extracellular vesicles (EVs) released by MSCs, may regenerate the IVD. The aim of this study was to investigate the therapeutic effects of Wharton's Jelly MSC (WJ\u2010MSC)\u2010derived EVs on human nucleus pulposus cells (hNPCs) using an in vitro 3D alginate\u2010bead culture model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      After EV isolation and characterization, hNPCs isolated from surgical specimens were encapsulated in alginate beads and treated with 10, 50, and 100\u2009\u03bcg\/mL WJ\u2010MSC\u2010EVs. Cell proliferation and viability were assessed by flow cytometry and live\/dead staining. Nitrite and glycosaminoglycan (GAG) content was evaluated through Griess and 1,9\u2010dimethylmethylene blue assays. hNPCs in alginate beads were paraffin\u2010embedded and stained for histological analysis (hematoxylin\u2013eosin and Alcian blue) to assess extracellular matrix (ECM) composition. Gene expression levels of catabolic (\n                      <jats:italic>MMP1, MMP13, ADAMTS5, IL6, NOS2<\/jats:italic>\n                      ), anabolic (\n                      <jats:italic>ACAN<\/jats:italic>\n                      ), and hNPC marker (\n                      <jats:italic>SOX9, KRT19<\/jats:italic>\n                      ) genes were analyzed through qPCR. Collagen type I and type II content was assessed with Western blot analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with WJ\u2010MSC\u2010EVs resulted in an increase in cell content and a decrease in cell death in degenerated hNPCs. Nitrite production was drastically reduced by EV treatment compared to the control. Furthermore, proteoglycan content was enhanced and confirmed by Alcian blue histological staining. EV stimulation attenuated ECM degradation and inflammation by suppressing catabolic and inflammatory gene expression levels. Additionally, NPC phenotypic marker genes were also maintained by the EV treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>WJ\u2010MSC\u2010derived EVs ameliorated hNPC growth and viability, and attenuated ECM degradation and oxidative stress, offering new opportunities for IVD regeneration as an attractive alternative strategy to cell therapy, which may be jeopardized by the harsh microenvironment of the IVD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsp2.1274","type":"journal-article","created":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T07:11:19Z","timestamp":1696662679000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Wharton's Jelly mesenchymal stromal cell\u2010derived extracellular vesicles promote nucleus pulposus cell anabolism in an in vitro\n                    <scp>3D<\/scp>\n                    alginate\u2010bead culture model"],"prefix":"10.1002","volume":"7","author":[{"given":"Veronica","family":"Tilotta","sequence":"first","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-1660","authenticated-orcid":false,"given":"Gianluca","family":"Vadal\u00e0","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"},{"name":"Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2424-1274","authenticated-orcid":false,"given":"Luca","family":"Ambrosio","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"},{"name":"Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Di Giacomo","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cicione","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Russo","sequence":"additional","affiliation":[{"name":"Laboratory for Regenerative Orthopaedics, Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery Universit\u00e0 Campus Bio\u2010Medico di Roma  Rome Italy"},{"name":"Operative Research Unit of Orthopaedic and Trauma Surgery Fondazione Policlinico Universitario Campus Bio\u2010Medico  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adas","family":"Darinskas","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Cancer Institute  Vilnius 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