{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T06:04:23Z","timestamp":1789365863047,"version":"build-2803163510"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Chronic lung allograft dysfunction (CLAD) remains the leading cause of late morbidity and mortality after lung transplantation, with limited therapeutic options. Mesenchymal stromal cells (MSCs) have immunomodulatory and regenerative properties that may have therapeutic potential in CLAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated the long-term safety and feasibility of repeated intravenous MSC administration in patients with advanced CLAD refractory to standard treatments. Six lung transplant patients with progressive moderate-to-severe CLAD received monthly infusions of allogeneic, bone marrow\u2013derived, HLA-unmatched MSCs (1\u2009\u00d7\u200910\u2076 cells\/kg). Safety was assessed by survival and infection incidence. Pulmonary function (FEV\u2081, FVC) and laboratory parameters were monitored longitudinally. Interrupted time-series analysis was used to evaluate changes in functional trends.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 251 MSC infusions were administered during the study period, with follow-up extending up to 58 months. All patients completed at least 24 months of follow-up. Survival at 24 months was 100%; one patient later died from pulmonary infection after being listed for retransplantation. MSC therapy was well tolerated, with no infusion-related toxicity, serious treatment-related adverse events or statistically significant increase in infection risk. While immediate changes in FEV\u2081 or FVC were not observed, the rate of functional decline significantly decreased post-treatment, suggesting a potential attenuation of functional decline. Laboratory parameters remained stable throughout follow-up, with no evidence of systemic toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Repeated long-term intravenous administration of allogeneic bone marrow- derived MSCs in patients with advanced, treatment-refractory CLAD appears feasible, safe, and generally well tolerated. Although no statistically significant increase in respiratory infection incidence was observed, the study was underpowered to exclude a clinically meaningful increase in infection risk. In our cohort, lung function decline appeared to stabilize in some patients following MSC initiation over time; however, the observed changes in lung function trajectories are exploratory and should not be interpreted as evidence of therapeutic efficacy. Controlled clinical trials are needed to clarify the potential role of MSC therapy and to define optimal treatment strategies and patient selection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1942517","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T05:39:22Z","timestamp":1789364362000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term monthly mesenchymal stromal cell therapy for advanced chronic lung allograft dysfunction: a single-centre safety and feasibility cohort study"],"prefix":"10.3389","volume":"13","author":[{"given":"Sara","family":"Lettieri","sequence":"first","affiliation":[{"name":"Pneumology Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]},{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, Pavia","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"Avanzini","sequence":"additional","affiliation":[{"name":"SSD Cell Factory and Center for Advanced Therapies, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]},{"name":"Pediatric Hematology\/Oncology Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica Federica","family":"Briganti","sequence":"additional","affiliation":[{"name":"Pneumology Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bozzini","sequence":"additional","affiliation":[{"name":"Second Department of Anesthesia and Intensive Care, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Bozza","sequence":"additional","affiliation":[{"name":"Pediatric Hematology\/Oncology Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Lenta","sequence":"additional","affiliation":[{"name":"SSD Cell Factory and Center for Advanced Therapies, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Vertui","sequence":"additional","affiliation":[{"name":"Pneumology Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]},{"name":"Department of Medical and Surgical Sciences (DiMEC), University of Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mariani","sequence":"additional","affiliation":[{"name":"Pneumology Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo Guido","family":"Corsico","sequence":"additional","affiliation":[{"name":"Pneumology Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]},{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, Pavia","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klodiana","family":"Mucaj","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, Pavia","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariachiara","family":"Crescenzi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, Pavia","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"De Silvestri","sequence":"additional","affiliation":[{"name":"Biometry Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Comoli","sequence":"additional","affiliation":[{"name":"SSD Cell Factory and Center for Advanced Therapies, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]},{"name":"Pediatric Hematology\/Oncology Unit, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Belliato","sequence":"additional","affiliation":[{"name":"Second Department of Anesthesia and Intensive Care, IRCCS San Matteo Hospital Foundation","place":["Pavia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Meloni","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine (DIMET), University of Piemonte Orientale UniUPO and IRCCS SS. 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