Cargando…
Engineered human mesenchymal stem cells for neuroblastoma therapeutics
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 ce...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549104/ https://www.ncbi.nlm.nih.gov/pubmed/31115546 http://dx.doi.org/10.3892/or.2019.7152 |
_version_ | 1783423937628078080 |
---|---|
author | Nieddu, Valentina Piredda, Roberta Bexell, Daniel Barton, Jack Anderson, John Sebire, Neil Kolluri, Krishna Janes, Sam M. Karteris, Emmanouil Sala, Arturo |
author_facet | Nieddu, Valentina Piredda, Roberta Bexell, Daniel Barton, Jack Anderson, John Sebire, Neil Kolluri, Krishna Janes, Sam M. Karteris, Emmanouil Sala, Arturo |
author_sort | Nieddu, Valentina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6549104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-65491042019-06-10 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 Oncol Rep Articles 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. D.A. Spandidos 2019-07 2019-05-08 /pmc/articles/PMC6549104/ /pubmed/31115546 http://dx.doi.org/10.3892/or.2019.7152 Text en Copyright: © Nieddu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Nieddu, Valentina Piredda, Roberta Bexell, Daniel Barton, Jack Anderson, John Sebire, Neil Kolluri, Krishna Janes, Sam M. Karteris, Emmanouil Sala, Arturo Engineered human mesenchymal stem cells for neuroblastoma therapeutics |
title | Engineered human mesenchymal stem cells for neuroblastoma therapeutics |
title_full | Engineered human mesenchymal stem cells for neuroblastoma therapeutics |
title_fullStr | Engineered human mesenchymal stem cells for neuroblastoma therapeutics |
title_full_unstemmed | Engineered human mesenchymal stem cells for neuroblastoma therapeutics |
title_short | Engineered human mesenchymal stem cells for neuroblastoma therapeutics |
title_sort | engineered human mesenchymal stem cells for neuroblastoma therapeutics |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549104/ https://www.ncbi.nlm.nih.gov/pubmed/31115546 http://dx.doi.org/10.3892/or.2019.7152 |
work_keys_str_mv | AT niedduvalentina engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT pireddaroberta engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT bexelldaniel engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT bartonjack engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT andersonjohn engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT sebireneil engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT kollurikrishna engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT janessamm engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT karterisemmanouil engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics AT salaarturo engineeredhumanmesenchymalstemcellsforneuroblastomatherapeutics |