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Tumoricidal bystander effect in the suicide gene therapy using mesenchymal stem cells does not injure normal brain tissues.

Abstract：

:In our previous rat study, an established intracranial C6 glioma was successfully treated using intratumoral injection of mesenchymal stem cells transduced with the herpes simplex virus-thymidine kinase gene (MSCtk) and systemic administration of ganciclovir (GCV). In the present study, effect of the "bystander effect" associated with the MSCtk/GCV strategy on the background normal brain tissues was examined in both in vitro and in vivo conditions. Rat MSCtk and C6 glioma cells were mixed and seeded on the rat primary neuron and glia co-culture in the medium containing GCV to generate the bystander effect and the numbers of background cells were counted on day 0, 2 and 7. Though the number of MSCtk and C6 cells decreased rapidly due to the bystander effect, most of the neurons and glias survived on day 7. Next, rats were intracranially injected with the MSCtk and C6 cells and then intraperitoneally administered with GCV for 7days. No remarkable histological abnormality including apoptosis was observed in the background brain tissues near the injection site. The present study has demonstrated that the tumoricidal bystander effect does not injure the background normal brain tissue significantly and that the suicide gene therapies are sufficiently safe.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Amano S,Gu C,Koizumi S,Tokuyama T,Namba H

doi

10.1016/j.canlet.2011.02.037

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

99-105

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(11)00132-7

journal_volume

306

pub_type

杂志文章

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