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Rat Multipotent Mesenchymal Stromal Cells Lack Long-Distance Tropism to 3 Different Rat Glioma Models

Bexell, Daniel LU ; Gunnarsson, Salina LU ; Svensson, Andreas LU ; Tormin, Ariane LU ; Henriques-Oliveira, Catarina; Siesjö, Peter LU ; Paul-Visse, Gesine LU ; Salford, Leif LU ; Scheding, Stefan LU and Bengzon, Johan LU (2012) In Neurosurgery 70(3). p.731-739
Abstract
BACKGROUND: Viral gene therapy of malignant brain tumors has been restricted by the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas, and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy. OBJECTIVE: To investigate MSC migration in detail after intratumoral and extratumoral implantation through syngeneic and orthotopic glioma models. METHODS: Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance from rat gliomas. RESULTS: We found no evidence of long-distance MSC migration through the intact... (More)
BACKGROUND: Viral gene therapy of malignant brain tumors has been restricted by the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas, and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy. OBJECTIVE: To investigate MSC migration in detail after intratumoral and extratumoral implantation through syngeneic and orthotopic glioma models. METHODS: Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance from rat gliomas. RESULTS: We found no evidence of long-distance MSC migration through the intact striatum toward syngeneic D74(RG2), N32, and N29 gliomas in the ipsilateral hemisphere or across the corpus callosum to gliomas located in the contralateral hemisphere. After intratumoral injection, MSCs migrated extensively, specifically within N32 gliomas. The MSCs did not proliferate within tumors, suggesting a low risk of malignant transformation of in vivo grafted cell vectors. Using a model for surgical glioma resection, we found that intratumorally grafted MSCs migrate efficiently within glioma remnants after partial surgical resection. CONCLUSION: The findings point to limitations for the use of MSCs as vectors in glioma gene therapy, although intratumoral MSC implantation provides a dense and tumor-specific vector distribution. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gene delivery, Glioma, Mesenchymal stem cell, Multipotent mesenchymal, stromal cell, Tumor
in
Neurosurgery
volume
70
issue
3
pages
731 - 739
publisher
Congress of Neurological Surgeons
external identifiers
  • wos:000300781700031
  • scopus:84866177104
ISSN
0148-396X
DOI
10.1227/NEU.0b013e318232dedd
language
English
LU publication?
yes
id
ec087e4c-b6b4-40a3-b8a0-7cff5dddb761 (old id 2379130)
date added to LUP
2012-04-02 09:20:13
date last changed
2017-10-01 04:19:23
@article{ec087e4c-b6b4-40a3-b8a0-7cff5dddb761,
  abstract     = {BACKGROUND: Viral gene therapy of malignant brain tumors has been restricted by the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas, and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy. OBJECTIVE: To investigate MSC migration in detail after intratumoral and extratumoral implantation through syngeneic and orthotopic glioma models. METHODS: Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance from rat gliomas. RESULTS: We found no evidence of long-distance MSC migration through the intact striatum toward syngeneic D74(RG2), N32, and N29 gliomas in the ipsilateral hemisphere or across the corpus callosum to gliomas located in the contralateral hemisphere. After intratumoral injection, MSCs migrated extensively, specifically within N32 gliomas. The MSCs did not proliferate within tumors, suggesting a low risk of malignant transformation of in vivo grafted cell vectors. Using a model for surgical glioma resection, we found that intratumorally grafted MSCs migrate efficiently within glioma remnants after partial surgical resection. CONCLUSION: The findings point to limitations for the use of MSCs as vectors in glioma gene therapy, although intratumoral MSC implantation provides a dense and tumor-specific vector distribution.},
  author       = {Bexell, Daniel and Gunnarsson, Salina and Svensson, Andreas and Tormin, Ariane and Henriques-Oliveira, Catarina and Siesjö, Peter and Paul-Visse, Gesine and Salford, Leif and Scheding, Stefan and Bengzon, Johan},
  issn         = {0148-396X},
  keyword      = {Gene delivery,Glioma,Mesenchymal stem cell,Multipotent mesenchymal,stromal cell,Tumor},
  language     = {eng},
  number       = {3},
  pages        = {731--739},
  publisher    = {Congress of Neurological Surgeons},
  series       = {Neurosurgery},
  title        = {Rat Multipotent Mesenchymal Stromal Cells Lack Long-Distance Tropism to 3 Different Rat Glioma Models},
  url          = {http://dx.doi.org/10.1227/NEU.0b013e318232dedd},
  volume       = {70},
  year         = {2012},
}