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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2009) 33, 466–474 (Printed in Great Britain)
Adenoviral-mediated interleukin-18 expression in mesenchymal stem cells effectively suppresses the growth of glioma in rats
Gang Xua, Xiao‑Dan Jianga, Ying Xub, Jing Zhangc, Fan‑Heng Huangd, Zhen‑Zhou Chena, De‑Xiang Zhoua, Jiang‑Hua Shanga, Yu‑Xi Zoua, Ying‑Qian Caia, Sheng‑Bin Koua, Yi‑Zhao Chena, Ru‑Xiang Xua* and Yan‑Jun Zengc*
aInstitute of Neuromedicine, South Medical University, Zhujiang Hospital, Guangzhou 510280, China
bInstitute of ophthalmology, Shan Yang Country people's Hospital, ShanXi 726400, China
cBiomechanics & Medical Information Institute, Beijing University of Technology, Beijing 100022, China
dInstitute of Medical Image center, South Medical University, Zhujiang Hospital, Guangzhou 510280, China


Abstract

Glioma is the most common primary intracranial malignant tumor. Despite advances in surgical techniques and adjuvant radio- and chemotherapies, the prognosis for patients with glioma remains poor. We have explored the effects of using genetically modified mesenchymal stem cells (MSCs) to treat malignant glioma in rats. Mesenchymal stem cells isolated from Sprague–Dawley rats can directly suppress the growth of C6 cells in vitro. MSCs transplanted intratumorally can also significantly inhibit the growth of glioma and prolong survival in C6 glioma-bearing models. MSCs producing Interleukin-18 infected by adenoviral vector inhibited glioma growth and prolonged the survival of glioma-bearing rats. Transplantation of IL-18 secreting MSCs was associated with enhanced T cell infiltration and long-term anti-tumor immunity. Thus, IL-18 may be an effective adoptive immunotherapy for malignant glioma. When used in conjunction with MSCs as targeting vehicles in vivo, IL-18 may offer a promising new treatment option for malignant glioma.


Key words: Glioma, Mesenchymal stem cell, Adenoviral vector, Interleukin-18.

*Corresponding authors.


Received 2 November 2007/7 April 2008; accepted 30 July 2008

doi:10.1016/j.cellbi.2008.07.023


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)