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Antitumor effect of
genetically engineered mesenchymal stem cells in a rat glioma model
K Nakamura, Y Ito, Y Kawano, K
Kurozumi, M Kobune, H Tsuda, A Bizen, O Honmou, Y Niitsu and H Hamada
Department of Molecular Medicine,
Sapporo Medical University, Sapporo, Japan [K.N., Y.I., Y.K., K.K., M.K., H.T.,
H.H.]; Division of Gene Therapy, Sapporo Medical University, Sapporo, Japan
[Y.I.]; 4th Department of Internal Medicine, Sapporo Medical University,
Sapporo, Japan [Y.K., M.K., Y.N.]; Department of Neurological Surgery, Field of
Neuroscience, Branch of Biophysical Science, Graduate School of Medicine and
Dentistry, Okayama University, Okayama, Japan [K.K.]; Department of
Neurosurgery, Sapporo Medical University, Sapporo, Japan [A.B., O.H.].
Correspondence to: Dr H Hamada, Department of Molecular Medicine, Sapporo
Medical University, South-1, West-17, Chuo-ku, Sapporo 060-8556, Japan.
Received 28 August 2003; accepted 3 February 2004; published online 13 May 2004
The prognosis of patients with
malignant glioma is extremely poor, despite the extensive surgical treatment
that they receive and recent improvements in adjuvant radio- and
chemotherapy.
In the present study, we propose the use of gene-modified mesenchymal stem cells
(MSCs) as a new tool for gene therapy of malignant brain neoplasms.
Primary MSCs isolated from Fischer 344 rats possessed excellent migratory
ability and exerted inhibitory effects on the proliferation of 9L glioma cell in
vitro.
We also confirmed the migratory capacity of MSCs in vivo and showed that
when they were inoculated into the contralateral hemisphere, they migrated
towards 9L glioma cells through the corpus callosum.
MSCs implanted directly into the tumor localized mainly at the border between
the 9L tumor cells and normal brain parenchyma, and also infiltrated into the
tumor bed.
Intratumoral injection of MSCs caused significant inhibition of 9L tumor growth
and increased the survival of 9L glioma-bearing rats.
Gene-modification of MSCs by infection with an adenoviral vector encoding human
interleukin-2 (IL-2) clearly augmented the antitumor effect and further
prolonged the survival of tumor-bearing rats.
Thus, gene therapy employing MSCs as a targeting vehicle would be promising as a
new therapeutic approach for refractory brain tumor.
Keywords: glioma; mesenchymal stem
cell; adenoviral vector; interleukin-2
© 2004 Nature Publishing Group
Source: http://www.nature.com/cgi-taf/DynaPage.taf?file=/gt/journal/v11/n14/abs/3302276a.html&dynoptions=doi1092206570
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