eprintid: 10075422 rev_number: 27 eprint_status: archive userid: 608 dir: disk0/10/07/54/22 datestamp: 2019-06-11 08:07:21 lastmod: 2021-12-06 00:19:05 status_changed: 2019-06-11 08:07:21 type: article metadata_visibility: show creators_name: Nieddu, V creators_name: Piredda, R creators_name: Bexell, D creators_name: Barton, J creators_name: Anderson, J creators_name: Sebire, N creators_name: Kolluri, K creators_name: Janes, SM creators_name: Karteris, E creators_name: Sala, A title: Engineered human mesenchymal stem cells for neuroblastoma therapeutics ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: K71 divisions: D13 divisions: G22 divisions: G25 keywords: mesenchymal stem cells, neuroblastoma, death receptors note: Copyright: © Nieddu et al. This is an open access article distributed under the terms of Creative Commons Attribution License. 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. date: 2019-05-08 date_type: published official_url: http://doi.org/10.3892/or.2019.7152 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1661152 doi: 10.3892/or.2019.7152 lyricists_name: Anderson, William lyricists_name: Janes, Samuel lyricists_name: Kolluri, Krishna lyricists_name: Sebire, Neil lyricists_id: JANDE86 lyricists_id: SMJAN15 lyricists_id: KKKOL90 lyricists_id: NJSEB45 actors_name: Kalinowski, Damian actors_id: DKALI47 actors_role: owner full_text_status: public publication: Oncology Reports volume: 42 pagerange: 35-42 event_location: Greece issn: 1791-2431 citation: Nieddu, V; Piredda, R; Bexell, D; Barton, J; Anderson, J; Sebire, N; Kolluri, K; ... Sala, A; + view all <#> Nieddu, V; Piredda, R; Bexell, D; Barton, J; Anderson, J; Sebire, N; Kolluri, K; Janes, SM; Karteris, E; Sala, A; - view fewer <#> (2019) Engineered human mesenchymal stem cells for neuroblastoma therapeutics. Oncology Reports , 42 pp. 35-42. 10.3892/or.2019.7152 <https://doi.org/10.3892/or.2019.7152>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10075422/1/Anderson_Engineered%20human%20mesenchymal%20stem%20cells%20for%20neuroblastoma%20therapeutics_VoR.pdf