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Toward Brain Tumor Gene Therapy Using Multipotent Mesenchymal Stromal Cell Vectors.

Bexell, Daniel LU ; Scheding, Stefan LU and Bengzon, Johan LU (2010) In Molecular Therapy May 4. p.1067-1075
Abstract
Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers. Implanted and injected multipotent mesenchymal stromal cells (MSCs) have shown tropism for several types of primary tumors and metastases. This capacity of MSCs forms the basis for their use as a gene vector system in neoplasms. Here, we review the tumor-directed migratory potential of MSCs, mechanisms of the migration, and the choice of therapeutic transgenes, with a focus on malignant gliomas as a model system for invasive and highly vascularized tumors. We examine recent findings demonstrating that MSCs share many... (More)
Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers. Implanted and injected multipotent mesenchymal stromal cells (MSCs) have shown tropism for several types of primary tumors and metastases. This capacity of MSCs forms the basis for their use as a gene vector system in neoplasms. Here, we review the tumor-directed migratory potential of MSCs, mechanisms of the migration, and the choice of therapeutic transgenes, with a focus on malignant gliomas as a model system for invasive and highly vascularized tumors. We examine recent findings demonstrating that MSCs share many characteristics with pericytes and that implanted MSCs localize primarily to perivascular niches within tumors, which might have therapeutic implications. The use of MSC vectors in cancer gene therapy raises concerns, however, including a possible MSC contribution to tumor stroma and vasculature, MSC-mediated antitumor immune suppression, and the potential malignant transformation of cultured MSCs. Nonetheless, we highlight the novel prospects of MSC-based tumor therapy, which appears to be a promising approach. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Therapy
volume
May 4
pages
1067 - 1075
publisher
Nature Publishing Group
external identifiers
  • wos:000278545800004
  • pmid:20407426
  • scopus:77953133974
ISSN
1525-0024
DOI
10.1038/mt.2010.58
language
English
LU publication?
yes
id
15e4687a-2549-489c-a39e-de29f10b2aed (old id 1594974)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20407426?dopt=Abstract
date added to LUP
2010-05-04 21:14:37
date last changed
2018-06-10 04:48:35
@article{15e4687a-2549-489c-a39e-de29f10b2aed,
  abstract     = {Gene therapy of solid cancers has been severely restricted by the limited distribution of vectors within tumors. However, cellular vectors have emerged as an effective migratory system for gene delivery to invasive cancers. Implanted and injected multipotent mesenchymal stromal cells (MSCs) have shown tropism for several types of primary tumors and metastases. This capacity of MSCs forms the basis for their use as a gene vector system in neoplasms. Here, we review the tumor-directed migratory potential of MSCs, mechanisms of the migration, and the choice of therapeutic transgenes, with a focus on malignant gliomas as a model system for invasive and highly vascularized tumors. We examine recent findings demonstrating that MSCs share many characteristics with pericytes and that implanted MSCs localize primarily to perivascular niches within tumors, which might have therapeutic implications. The use of MSC vectors in cancer gene therapy raises concerns, however, including a possible MSC contribution to tumor stroma and vasculature, MSC-mediated antitumor immune suppression, and the potential malignant transformation of cultured MSCs. Nonetheless, we highlight the novel prospects of MSC-based tumor therapy, which appears to be a promising approach.},
  author       = {Bexell, Daniel and Scheding, Stefan and Bengzon, Johan},
  issn         = {1525-0024},
  language     = {eng},
  pages        = {1067--1075},
  publisher    = {Nature Publishing Group},
  series       = {Molecular Therapy},
  title        = {Toward Brain Tumor Gene Therapy Using Multipotent Mesenchymal Stromal Cell Vectors.},
  url          = {http://dx.doi.org/10.1038/mt.2010.58},
  volume       = {May 4},
  year         = {2010},
}