Inhibition of human malignant pleural mesothelioma growth by mesenchymal stromal cells

V. Coccè, S. La Monica, M. Bonelli, G. Alessandri, R. Alfieri, C.A. Lagrasta, D. Madeddu, C. Frati, L. Flammini, D. Lisini, A. Marcianti, E. Parati, F. Paino, A. Giannì, G. Farronato, A. Falco, L. Spaggiari, F. Petrella, A. Pessina

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1427
Issue number6
Publication statusPublished - 2021


  • Cell therapy
  • Malignant pleural mesothelioma (MPM)
  • Mesenchymal stromal cells
  • Mesothelioma
  • caspase 3
  • caspase 9
  • CD146 antigen
  • CD34 antigen
  • doxorubicin
  • fibroblast growth factor
  • fibronectin
  • fluorouracil
  • gamma interferon
  • gemcitabine
  • hydrogel
  • interleukin 10
  • interleukin 1beta
  • interleukin 6
  • oxaliplatin
  • paclitaxel
  • phosphatidylserine
  • platelet endothelial cell adhesion molecule 1
  • protein Bax
  • Thy 1 membrane glycoprotein
  • tubulin
  • tumor necrosis factor
  • vasculotropin
  • adipose tissue
  • ADSC cell line
  • animal cell
  • animal experiment
  • animal model
  • antineoplastic activity
  • antiproliferative activity
  • apoptosis
  • Article
  • cancer chemotherapy
  • cancer growth
  • cancer inhibition
  • cancer prognosis
  • cancer therapy
  • cell cycle arrest
  • cell death
  • cell lysate
  • cell proliferation
  • cell viability
  • clinical article
  • controlled study
  • cytokine production
  • dendritic cell
  • female
  • flow cytometry
  • fluorescence microscopy
  • histology
  • human
  • human cell
  • immunofluorescence
  • immunohistochemistry
  • in vitro study
  • in vivo study
  • mesenchymal stroma cell
  • mesothelioma cell line
  • mouse
  • MTT assay
  • nonhuman
  • pleura mesothelioma
  • secretomics
  • T lymphocyte
  • transwell assay
  • tumor growth
  • tumor microenvironment
  • tumor xenograft
  • adolescent
  • adult
  • aged
  • animal
  • Bagg albino mouse
  • cell cycle
  • cell survival
  • mesenchymal stem cell
  • mesothelioma
  • middle aged
  • pathology
  • tumor cell line
  • young adult
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Female
  • Humans
  • Mesenchymal Stem Cells
  • Mesothelioma, Malignant
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Young Adult


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