{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:25:55Z","timestamp":1783038355249,"version":"3.54.6"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:00:00Z","timestamp":1695340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIFA Ricerca Indipendente","award":["2016-02364623"],"award-info":[{"award-number":["2016-02364623"]}]},{"name":"AIFA Ricerca Indipendente","award":["2016-02364623"],"award-info":[{"award-number":["2016-02364623"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Severe forms of idiopathic nephrotic syndrome (INS) require prolonged immunosuppressive therapies and repeated courses of high-dose glucocorticoids. Mesenchymal stromal cells (MSCs) have promising immunomodulatory properties that may be employed therapeutically to reduce patient exposure to medications and their side effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We performed a phase I open-label trial assessing safety and feasibility of autologous bone marrow\u2013derived MSCs (BM-MSCs) in children and young adults with severe forms of steroid-dependent nephrotic syndrome. Following autologous BM-MSC preparation and infusion, oral immunosuppression was tapered. Safety, efficacy, and immunomodulatory effects in vivo were monitored for 12 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Sixteen patients (10 children, 6 adults) were treated. Adverse events were limited and not related to BM-MSC infusions. All patients relapsed during follow-up, but in the 10 treated children, time to first relapse was delayed (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.02) and number of relapses was reduced (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.002) after BM-MSC infusion, compared with the previous 12 months. Cumulative prednisone dose was also reduced at 12 months compared with baseline (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05). No treatment benefit was observed in adults.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>In children, despite tapering of immunosuppression, clinical benefit was mirrored by a significant reduction in total CD19+, mature, and memory B cells and an increase in regulatory T cells in vivo up to 3\u20136 months following BM-MSC infusion<\/jats:title>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Treatment with autologous BM-MSCs is feasible and safely reduces relapses and immunosuppression at 12 months in children with severe steroid-dependent INS. Immunomodulatory studies suggest that repeating MSC infusions at 3\u20136 months may sustain benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>EudraCT 2016-004804-77.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>AIFA Ricerca Indipendente 2016-02364623.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.169424","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T12:01:34Z","timestamp":1691668894000},"source":"Crossref","is-referenced-by-count":13,"title":["A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome"],"prefix":"10.1172","volume":"8","author":[{"given":"Marina","family":"Vivarelli","sequence":"first","affiliation":[{"name":"Division of Nephrology, and"},{"name":"Laboratory of Nephrology, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Colucci","sequence":"additional","affiliation":[{"name":"Laboratory of Nephrology, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Algeri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\/Oncology and Cell and Gene Therapy, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, Rome, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Zotta","sequence":"additional","affiliation":[{"name":"Division of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0383-3468","authenticated-orcid":true,"given":"Francesco","family":"Emma","sequence":"additional","affiliation":[{"name":"Division of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"L\u2019Erario","sequence":"additional","affiliation":[{"name":"Division of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3150-6704","authenticated-orcid":true,"given":"Marco","family":"Busutti","sequence":"additional","affiliation":[{"name":"Division of Nephrology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Rota","sequence":"additional","affiliation":[{"name":"Unit of Nephrology and Dialysis, Azienda Socio Sanitaria Territoriale (ASST), Bergamo, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-1541","authenticated-orcid":true,"given":"Chiara","family":"Capelli","sequence":"additional","affiliation":[{"name":"Center of Cellular Therapy \u201cG. 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