Preclinical analysis of human mesenchymal stem cells: tumor tropism and therapeutic efficiency of local HSV-TK suicide gene therapy in glioblastoma.
brain tumor
gene therapy
glioblastoma
migration
stem cells
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
22 Oct 2019
22 Oct 2019
Historique:
received:
27
01
2019
accepted:
19
06
2019
entrez:
7
11
2019
pubmed:
7
11
2019
medline:
7
11
2019
Statut:
epublish
Résumé
Glioblastoma are highly invasive and associated with limited therapeutic options and a grim prognosis. Using stem cells to extend current therapeutic strategies by targeted drug delivery to infiltrated tumors cells is highly attractive. This study analyzes the tumor homing and therapeutic abilities of clinical grade human mesenchymal stem cells (MSCs) in an orthotopic glioblastoma mouse model. Our time course analysis demonstrated that MSCs display a rapid targeted migration to intracerebral U87 glioma xenografts growing in the contralateral hemisphere within the first 48h hours after application as assessed by histology and 7T magnetic resonance imaging. MSCs accumulated predominantly peritumorally but also infiltrated the main tumor mass and targeted distant tumor satellites while no MSCs were found in other regions of the brain. Intratumoral application of MSCs expressing herpes simplex virus thymidine kinase followed by systemic prodrug application of ganciclovir led to a significant tumor growth inhibition of 86% versus the control groups (p<0.05), which translated in a significant prolonged survival time (p<0.05). This study demonstrates that human MSCs generated according to apceth's GMP process from healthy donors are able to target and provide a significant growth inhibition in a glioblastoma model supporting a potential clinical translation.
Identifiants
pubmed: 31692882
doi: 10.18632/oncotarget.27071
pii: 27071
pmc: PMC6817450
doi:
Types de publication
Journal Article
Langues
eng
Pagination
6049-6061Informations de copyright
Copyright: © 2019 Dührsen et al.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST NOS received funding from Apceth Biopharma to perform in vivo studies. DH, SG, CG and FGH are employees of Apceth Biopharma.
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