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Engineered human mesenchymal stem cells for neuroblastoma therapeutics

Nieddu, Valentina ; Piredda, Roberta ; Bexell, Daniel LU ; Barton, Jack ; Anderson, John ; Sebire, Neil ; Kolluri, Krishna ; Janes, Sam M. ; Karteris, Emmanouil and Sala, Arturo (2019) In Oncology Reports 42(1). p.35-42
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... (More)

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 xenotrans-plantation 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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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Death receptors, Mesenchymal stem cells, Neuroblastoma
in
Oncology Reports
volume
42
issue
1
pages
8 pages
publisher
Spandidos Publications
external identifiers
  • pmid:31115546
  • scopus:85066750015
ISSN
1021-335X
DOI
10.3892/or.2019.7152
language
English
LU publication?
yes
id
7c6dbecb-6125-46df-8a79-e35b13a452fb
date added to LUP
2019-07-01 14:11:54
date last changed
2024-06-11 20:58:18
@article{7c6dbecb-6125-46df-8a79-e35b13a452fb,
  abstract     = {{<p>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 xenotrans-plantation 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.</p>}},
  author       = {{Nieddu, Valentina and Piredda, Roberta and Bexell, Daniel and Barton, Jack and Anderson, John and Sebire, Neil and Kolluri, Krishna and Janes, Sam M. and Karteris, Emmanouil and Sala, Arturo}},
  issn         = {{1021-335X}},
  keywords     = {{Death receptors; Mesenchymal stem cells; Neuroblastoma}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{35--42}},
  publisher    = {{Spandidos Publications}},
  series       = {{Oncology Reports}},
  title        = {{Engineered human mesenchymal stem cells for neuroblastoma therapeutics}},
  url          = {{http://dx.doi.org/10.3892/or.2019.7152}},
  doi          = {{10.3892/or.2019.7152}},
  volume       = {{42}},
  year         = {{2019}},
}