Engineered human mesenchymal stem cells for neuroblastoma therapeutics

Nieddu,Valentina; Piredda,Roberta; Bexell,Daniel; Barton,Jack; Anderson,John; Sebire,Neil; Kolluri,Krishna; Janes,Sam   M.; Karteris,Emmanouil; Sala,Arturo

doi:10.3892/or.2019.7152

Engineered human mesenchymal stem cells for neuroblastoma therapeutics

Authors:
- Valentina Nieddu
- Roberta Piredda
- Daniel Bexell
- Jack Barton
- John Anderson
- Neil Sebire
- Krishna Kolluri
- Sam M. Janes
- Emmanouil Karteris
- Arturo Sala
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Affiliations: Department of Life Sciences, Research Institute of Environment, Health and Societies, Brunel University London, Uxbridge, Middlesex UB8 3PH, UK, Department of Laboratory Medicine, Translational Cancer Research, Lund University, SE-221 00 Lund, Sweden, Institute of Child Health, Unit of Molecular Haematology and Cancer Biology, University College London, London WC1N 1EH, UK, Developmental Biology and Cancer Programme, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, UK, Lungs for Living Research Centre, UCL Respiratory, University College London, London WC1E 6JF, UK
Published online on: May 8, 2019 https://doi.org/10.3892/or.2019.7152
Pages: 35-42
Copyright: © Nieddu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Drug-resistant neuroblastoma remains a major challenge in paediatric oncology and novel and less toxic therapeutic approaches are urgently needed to improve survival and reduce the side effects of traditional therapeutic interventions. Mesenchymal stem cells (MSCs) are an attractive candidate for cell and gene therapy since they are recruited by and able to infiltrate tumours. This feature has been exploited by creating genetically modified MSCs that are able to combat cancer by delivering therapeutic molecules. Whether neuroblastomas attract systemically delivered MSCs is still controversial. We investigated whether MSCs engineered to express tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) could: i) cause death of classic and primary neuroblastoma cell lines in vitro; ii) migrate to tumour sites in vivo; and iii) reduce neuroblastoma growth in xenotransplantation experiments. We observed that classic and primary neuroblastoma cell lines expressing death receptors could be killed by TRAIL-loaded MSCs in vitro. When injected in the peritoneum of neuroblastoma-bearing mice, TRAIL-MSCs migrated to tumour sites, but were unable to change the course of cancer development. These results indicated that MSCs have the potential to be used to deliver drugs in neuroblastoma patients, but more effective biopharmaceuticals should be used instead of TRAIL.

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