{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T19:35:30Z","timestamp":1773689730934,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Malignant Pleural Mesothelioma (MPM) is an aggressive tumor that has a significant incidence related to asbestos exposure with no effective therapy and poor prognosis. The role of mesenchymal stromal cells (MSCs) in cancer is controversial due to their opposite effects on tumor growth and in particular, only a few data are reported on MSCs and MPM. Methods: We investigated the in vitro efficacy of adipose tissue-derived MSCs, their lysates and secretome against different MPM cell lines. After large-scale production of MSCs in a bioreactor, their efficacy was also evaluated on a human MPM xenograft in mice. Results: MSCs, their lysate and secretome inhibited MPM cell proliferation in vitro with S or G0\/G1 arrest of the cell cycle, respectively. MSC lysate induced cell death by apoptosis. The efficacy of MSC was confirmed in vivo by a significant inhibition of tumor growth, similar to that produced by systemic administration of paclitaxel. Interestingly, no tumor progression was observed after the last MSC treatment, while tumors started to grow again after stopping chemotherapeutic treatment. Conclusions: These data demonstrated for the first time that MSCs, both through paracrine and cell-to-cell interaction mechanisms, induced a significant inhibition of human mesothelioma growth. Since the prognosis for MPM patients is poor and the options of care are limited to chemotherapy, MSCs could provide a potential new therapeutic approach for this malignancy.<\/jats:p>","DOI":"10.3390\/cells10061427","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T12:08:55Z","timestamp":1623154135000},"page":"1427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-9529","authenticated-orcid":false,"given":"Valentina","family":"Cocc\u00e8","sequence":"first","affiliation":[{"name":"CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3578-3917","authenticated-orcid":false,"given":"Silvia","family":"La Monica","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5728-7899","authenticated-orcid":false,"given":"Mara","family":"Bonelli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Alessandri","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, Section of Microbiology and Virology, Medical School, University of Brescia, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0601-7244","authenticated-orcid":false,"given":"Roberta","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Costanza Annamaria","family":"Lagrasta","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Madeddu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Frati","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Flammini","sequence":"additional","affiliation":[{"name":"Food and Drug Department, University of Parma, 43124 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7436-8401","authenticated-orcid":false,"given":"Daniela","family":"Lisini","sequence":"additional","affiliation":[{"name":"Cell Therapy Production Unit-UPTC, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Marcianti","sequence":"additional","affiliation":[{"name":"Cell Therapy Production Unit-UPTC, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenio","family":"Parati","sequence":"additional","affiliation":[{"name":"IRCCS Istituti Clinici Scientifici Maugeri, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-1888","authenticated-orcid":false,"given":"Francesca","family":"Paino","sequence":"additional","affiliation":[{"name":"CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5983-9674","authenticated-orcid":false,"given":"Aldo","family":"Giann\u00ec","sequence":"additional","affiliation":[{"name":"CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"},{"name":"Maxillo-Facial and Dental Unit, Fondazione Ca\u2019 Granda IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giampietro","family":"Farronato","sequence":"additional","affiliation":[{"name":"Maxillo-Facial and Dental Unit, Fondazione Ca\u2019 Granda IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Unit of Orthodontics and Paediatric Dentistry, Fondazione Ca\u2019 Granda IRCCS Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Falco","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Spaggiari","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, IRCCS European Institute of Oncology, 20139 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-1576","authenticated-orcid":false,"given":"Francesco","family":"Petrella","sequence":"additional","affiliation":[{"name":"CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"},{"name":"Department of Thoracic Surgery, IRCCS European Institute of Oncology, 20139 Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto","family":"Pessina","sequence":"additional","affiliation":[{"name":"CRC StaMeTec, Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/jcp.22724","article-title":"Malignant mesothelioma: Facts, myths, and hypotheses","volume":"227","author":"Carbone","year":"2012","journal-title":"J. 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