Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells

Our plain-English summary of Paclitaxel-releasing mesenchymal stromal cells inhibit in vitro proliferation of human mesothelioma cells, by F. Petrella, V. Coccè, C. Masia, et al (Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie, 2017).

The study

• Authors: F. Petrella, V. Coccè, C. Masia, M. Milani, E.O. Salè, G. Alessandri, E. Parati, F. Sisto, F. Pentimalli, A.T. Brini, A. Pessina, L. Spaggiari
• Journal: Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
• Published: 2017;87:755-758
• Cited by: 39 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Malignant pleural mesothelioma (MPM) is a rare fatal asbestos-related malignancy originating in the mesothelial cells of the pleura. A platinum-based doublet containing a third-generation antifolate is the front-line standard of care whilst there are no approved second-line treatments for MPM which remains a disease setting to test the efficacy of new therapeutic agents.

Methods: Bone marrow mesenchymal stromal cells (BM-MSCs) were loaded with pemetrexed (PMX) and paclitaxel (PTX) according to a standardized procedure. Drug release by both PMX- and PTX-primed BM-MSCs (BM-MSCs/PMX and BM-MSCs/PTX) was tested on the in vitro proliferation of a panel of tumor cell lines including NCI-H28 mesothelioma.

Results: The in vitro anticancer activity of pure PTX was significantly higher than that of PMX against all the cell lines tested (14.7 times higher than that of PMX against NCI-H28). Whereas BM-MSCs did not take up and release PMX in amounts effective on mesothelioma, PTX-loaded BM-MSCs dramatically inhibited mesothelioma proliferation.

Conclusions: PTX-primed mesenchymal stromal cells successfully inhibit the in vitro proliferation of human mesothelioma cells. Further studies and in vivo testing are required to confirm our preliminary in vitro results as a potential new mesothelioma therapy based on cell drug delivery.

Copyright © 2017 Elsevier Masson SAS. All rights reserved.

In plain English

This short laboratory report from Milan, Italy, tested cells grown in the laboratory (in vitro), not patients. It did not study asbestos exposure. The authors loaded human bone marrow mesenchymal stromal cells, a type of support cell, with one of two cancer drugs, pemetrexed or paclitaxel, to see whether the cells could take up and release the drug. They measured the effect on the growth of a malignant pleural mesothelioma cell line called NCI-H28, a pancreatic cancer cell line used as a standard, and several other tumor cell lines. Used directly, paclitaxel inhibited growth more strongly than pemetrexed. Against NCI-H28 and the pancreatic line it was reported as about 13 times more active; the abstract gives 14.7 times for NCI-H28. Material from cells loaded with pemetrexed showed no inhibitory activity. Material from cells loaded with paclitaxel showed significant antitumor activity, with an estimated release of about 0.15 pg of paclitaxel per cell. The authors concluded that paclitaxel-loaded stromal cells inhibited mesothelioma cell growth in the laboratory. They said the finding awaits confirmation in vivo (in living organisms).

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment, published as a short communication
• Who was studied: No people or animals were studied. The tumor cells were the malignant pleural mesothelioma (MPM) cell line NCI-H28, which the discussion calls biphasic MPM, and the pancreatic adenocarcinoma line CFPAC-1, used as a standard model. A wider panel of tumor cell lines was also tested: T98G (glioblastoma multiforme), U87MG (likely glioblastoma), UPCI-SCC-154 (squamous oral carcinoma) and MOLT-4 (acute lymphoblastic leukemia). The drug carrier cells were stromal cells prepared from human bone marrow purchased from Lonza (Allendale, NJ, USA).
• Exposure: The cells were exposed to two chemotherapy drugs, pemetrexed (PMX) and paclitaxel (PTX), given either directly or released from drug-loaded bone marrow stromal cells (tested as cell lysates on NCI-H28 and CFPAC-1). Growth inhibition was measured with a 7-day MTT assay. No asbestos fibers were studied.
• Main results:
  • Used directly, both drugs produced a significant (p less than 0.001) dose-dependent inhibition of the tumor cell lines. Paclitaxel was more active, with the ratio between the two drugs' 50% inhibitory concentrations ranging from 13 to 100.
  • Against the pancreatic line CFPAC-1 and the mesothelioma line NCI-H28, paclitaxel's activity was about 13 times higher than pemetrexed's. The abstract gives 14.7 times for NCI-H28.
  • Lysate from stromal cells loaded with pemetrexed showed no inhibitory activity against either the mesothelioma cells or the pancreatic cancer cells.
  • Lysate from stromal cells loaded with paclitaxel showed significant antitumor activity on NCI-H28 and CFPAC-1 cells.
  • By comparing pure paclitaxel with the lysate, the authors estimated that each loaded cell delivered a mean of about 0.15 pg of paclitaxel.
  • This was a calculated projection, not a measurement. The authors assumed that if one million cells reached each cubic centimeter of tumor, the paclitaxel concentration would be about 150 ng/ml, which is 26 times the 50% inhibitory concentration found in vitro.
• The authors' conclusion: The authors concluded that paclitaxel-loaded stromal cells showed a strong capacity to inhibit mesothelioma cell growth. In their view this was the best in vitro drug-plus-cell combination for this disease. They also concluded that the stromal cells could not take up and release pemetrexed.
• Limitations the authors state:
  • The authors described their results as preliminary and in vitro only. They said further studies and in vivo testing are needed to show any effect on tumor progression.
  • The authors stated that the paclitaxel finding awaits confirmation in vivo.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Pleural Mesothelioma, Mesothelial Cells, Pleura, Antifolate, Pemetrexed (Alimta).

Related studies

• Inhibition of Human Malignant Pleural Mesothelioma Growth by Mesenchymal Stromal Cells — V. Coccè, S. La Monica, et al. (2021)
• Uptake-release by MSCs of a cationic platinum(II) complex active in vitro on human malignant cancer cell lines — I. Rimoldi, V. Coccè, et al. (2018)
• Antitumor effects of TRAIL-expressing mesenchymal stromal cells in a mouse xenograft model of human mesothelioma — M.J. Lathrop, E.K. Sage, et al. (2015)
• Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design — G.M. Stella, D. Lisini, et al. (2024)
• Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of human malignant pleural mesothelioma — T. Villanova, I. Gesmundo, et al. (2019)
• Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo — T. Tatsuta, T. Satoh, et al. (2018)

Browse more research in Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie, or return to medical research.