Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma

Elizabeth K Sage, Krishna K Kolluri, Katrina McNulty, Sofia Da Silva Lourenco, Tammy L Kalber, Katherine L Ordidge, Derek Davies, Y C Gary Lee, Adam Giangreco, Sam M Janes

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


Malignant pleural mesothelioma is a rare but devastating cancer of the pleural lining with no effective treatment. The tumour is often diffusely spread throughout the chest cavity, making surgical resection difficult, while systemic chemotherapy offers limited benefit. Bone marrow-derived mesenchymal stem cells (MSCs) home to and incorporate into tumour stroma, making them good candidates to deliver anticancer therapies. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic molecule that selectively induces apoptosis in cancer cells, leaving healthy cells unaffected. We hypothesised that human MSCs expressing TRAIL (MSCTRAIL) would home to an in vivo model of malignant pleural mesothelioma and reduce tumour growth. Human MSCs transduced with a lentiviral vector encoding TRAIL were shown in vitro to kill multiple malignant mesothelioma cell lines as predicted by sensitivity to recombinant TRAIL (rTRAIL). In vivo MSC homing was delineated using dual fluorescence and bioluminescent imaging, and we observed that higher levels of MSC engraftment occur after intravenous delivery compared with intrapleural delivery of MSCs. Finally, we show that intravenous delivery of MSCTRAIL results in a reduction in malignant pleural mesothelioma tumour growth in vivo via an increase in tumour cell apoptosis.

Original languageEnglish
Pages (from-to)638-47
Number of pages10
Issue number7
Publication statusPrint publication - Jul 2014
Externally publishedYes


  • Administration, Topical
  • Animals
  • Apoptosis/drug effects
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Infusions, Intravenous
  • Lung Neoplasms/metabolism
  • Mesenchymal Stem Cell Transplantation/methods
  • Mesenchymal Stem Cells/metabolism
  • Mesothelioma/metabolism
  • Mesothelioma, Malignant
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Pleural Neoplasms/metabolism
  • TNF-Related Apoptosis-Inducing Ligand/metabolism
  • Transfection
  • Tumor Burden/drug effects
  • Tumor Cells, Cultured


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