Bone Marrow Multipotent Mesenchymal Stroma Cells Act as Pericyte-like Migratory Vehicles in Experimental Gliomas.
(2009) In Molecular Therapy 2008(Nov 4.). p.183-190- Abstract
- Bone marrow-derived multipotent mesenchymal stroma cells (MSCs) have emerged as cellular vectors for gene therapy of solid cancers. We implanted enhanced green fluorescent protein-expressing rat MSCs directly into rat malignant gliomas to address their migratory capacity, phenotype, and effects on tumor neovascularization and animal survival. A single intratumoral injection of MSCs infiltrated the majority of invasive glioma extensions (72 +/- 14%) and a substantial fraction of distant tumor microsatellites (32 +/- 6%). MSC migration was highly specific for tumor tissue. Grafted MSCs integrated into tumor vessel walls and expressed pericyte markers alpha-smooth muscle actin, neuron-glia 2, and platelet-derived growth factor receptor-beta... (More)
- Bone marrow-derived multipotent mesenchymal stroma cells (MSCs) have emerged as cellular vectors for gene therapy of solid cancers. We implanted enhanced green fluorescent protein-expressing rat MSCs directly into rat malignant gliomas to address their migratory capacity, phenotype, and effects on tumor neovascularization and animal survival. A single intratumoral injection of MSCs infiltrated the majority of invasive glioma extensions (72 +/- 14%) and a substantial fraction of distant tumor microsatellites (32 +/- 6%). MSC migration was highly specific for tumor tissue. Grafted MSCs integrated into tumor vessel walls and expressed pericyte markers alpha-smooth muscle actin, neuron-glia 2, and platelet-derived growth factor receptor-beta but not endothelial cell markers. The pericyte marker expression profile and perivascular location of grafted MSCs indicate that these cells act as pericytes within tumors. MSC grafting did not influence tumor microvessel density or survival of tumor-bearing animals. The antiangiogenic drug Sunitinib markedly reduced the numbers of grafted MSCs migrating within tumors. We found no MSCs within gliomas following intravenous (i.v.) injections. Thus, MSCs should be administered by intratumoral implantations rather than by i.v. injections. Intratumorally grafted pericyte-like MSCs might represent a particularly well-suited vector system for delivering molecules to affect tumor angiogenesis and for targeting cancer stem cells within the perivascular niche.Molecular Therapy (2008); doi:10.1038/mt.2008.229. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1271826
- author
- Bexell, Daniel LU ; Gunnarsson, Salina LU ; Tormin, Ariane LU ; Darabi, Anna LU ; Gisselsson Nord, David LU ; Roybon, Laurent LU ; Scheding, Stefan LU and Bengzon, Johan LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Therapy
- volume
- 2008
- issue
- Nov 4.
- pages
- 183 - 190
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000262137100025
- pmid:18985030
- scopus:58149235124
- pmid:18985030
- ISSN
- 1525-0024
- DOI
- 10.1038/mt.2008.229
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neurosurgery (013026000), Hematology/Transplantation (013022014), Division of Clinical Genetics (013022003), Neuronal Survival (013212041)
- id
- 80ec6c38-2574-4a15-a460-659a23f07086 (old id 1271826)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18985030?dopt=Abstract
- date added to LUP
- 2016-04-01 11:42:29
- date last changed
- 2022-07-22 02:42:03
@article{80ec6c38-2574-4a15-a460-659a23f07086,
abstract = {{Bone marrow-derived multipotent mesenchymal stroma cells (MSCs) have emerged as cellular vectors for gene therapy of solid cancers. We implanted enhanced green fluorescent protein-expressing rat MSCs directly into rat malignant gliomas to address their migratory capacity, phenotype, and effects on tumor neovascularization and animal survival. A single intratumoral injection of MSCs infiltrated the majority of invasive glioma extensions (72 +/- 14%) and a substantial fraction of distant tumor microsatellites (32 +/- 6%). MSC migration was highly specific for tumor tissue. Grafted MSCs integrated into tumor vessel walls and expressed pericyte markers alpha-smooth muscle actin, neuron-glia 2, and platelet-derived growth factor receptor-beta but not endothelial cell markers. The pericyte marker expression profile and perivascular location of grafted MSCs indicate that these cells act as pericytes within tumors. MSC grafting did not influence tumor microvessel density or survival of tumor-bearing animals. The antiangiogenic drug Sunitinib markedly reduced the numbers of grafted MSCs migrating within tumors. We found no MSCs within gliomas following intravenous (i.v.) injections. Thus, MSCs should be administered by intratumoral implantations rather than by i.v. injections. Intratumorally grafted pericyte-like MSCs might represent a particularly well-suited vector system for delivering molecules to affect tumor angiogenesis and for targeting cancer stem cells within the perivascular niche.Molecular Therapy (2008); doi:10.1038/mt.2008.229.}},
author = {{Bexell, Daniel and Gunnarsson, Salina and Tormin, Ariane and Darabi, Anna and Gisselsson Nord, David and Roybon, Laurent and Scheding, Stefan and Bengzon, Johan}},
issn = {{1525-0024}},
language = {{eng}},
number = {{Nov 4.}},
pages = {{183--190}},
publisher = {{Nature Publishing Group}},
series = {{Molecular Therapy}},
title = {{Bone Marrow Multipotent Mesenchymal Stroma Cells Act as Pericyte-like Migratory Vehicles in Experimental Gliomas.}},
url = {{http://dx.doi.org/10.1038/mt.2008.229}},
doi = {{10.1038/mt.2008.229}},
volume = {{2008}},
year = {{2009}},
}