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

Biomed Pharmacother. 2017 Mar:87:755-758. doi: 10.1016/j.biopha.2017.01.118. Epub 2017 Jan 30.

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.

Keywords: Cell drug delivery; Mesenchymal stromal cells; Mesothelioma; Paclitaxel; Pemetrexed.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Humans
  • Lung Neoplasms / drug therapy*
  • Mesenchymal Stem Cells / drug effects*
  • Mesothelioma / drug therapy*
  • Mesothelioma, Malignant
  • Paclitaxel / pharmacology*
  • Pemetrexed / pharmacology

Substances

  • Antineoplastic Agents
  • Pemetrexed
  • Paclitaxel