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Bone Marrow Multipotent Mesenchymal Stroma Cells Act as Pericyte-like Migratory Vehicles in Experimental Gliomas.

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 (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)
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author
; ; ; ; ; ; and
organization
publishing date
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
2021-09-15 02:35:53
@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},
}