Research article summary (published 30 Aug 2009):

Dual-targeted antitumor effects against brainstem glioma by intravenous delivery of tumor necrosis factor-related, apoptosis-inducing, ligand-engineered human mesenchymal stem cells.

Full Abstract

OBJECTIVE: We sought to explore the dual-targeted antitumor effects of membrane-spanned, tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL)-engineered human mesenchymal stem cells (hMSCs) against brainstem gliomas. METHODS: The migration capacity of hMSCs toward gliomas was studied by the Transwell system in vitro and by intravenous injection of hMSCs in glioma-bearing mice in vivo. MSCs were engineered with native full-length human TRAIL (hTRAIL) by a recombinant adeno-associated virus (rAAV) vector (rAAV-hTRAIL). The targeted antiglioma effect was analyzed by coculture of hTRAIL-engineered MSCs with glioma in vitro and by systematic delivery of hTRAIL-engineered MSCs to established human brainstem glioma xenografts. RESULTS: We demonstrated systematically that transplanted MSCs migrated to a brainstem glioma with a high specificity. MSCs penetrated the vessels surrounding the tumor, then streamed in a chain pattern toward the glioma, eventually surrounding the tumor. Membrane-spanned, TRAIL-engineered MSCs not only expressed full-length TRAIL in MSC surface, but secreted some soluble TRAIL in medium. After being infected with rAAV-hTRAIL, hMSCs showed no increase in apoptosis. After coculture of hTRAIL-engineered MSCs and U87MG cells, the apoptosis of U87MG cells significantly increased more than soluble TRAIL-treated U87MG cells. Systematic delivery of hTRAIL-engineered MSCs to established human brainstem glioma xenografts resulted in the potent induction of apoptosis in gliomas, but not in normal brain and prolonged survival to 38.0 +/- 10.46 days compared with phosphate-buffered saline (16.0 +/- 0.66 days), soluble TRAIL (19.0 +/- 1.65 days), and hMSC-LacZ (14.0 +/- 0.59 days) treated groups. CONCLUSION: Systematically transplanted MSCs migrated to gliomas with a high specificity. Systematic delivery of MSC-hTRAIL can prolong the survival of brainstem glioma-bearing mice, presumably through a dual-targeted effect of membrane-spanned, TRAIL-engineered MSCs in the tumor microenvironment. MSCs may be an effective vehicle for the targeted delivery of therapeutic agents to brainstem gliomas.

Author information

Author/s: Yang, Bojie (B); Wu, Xing (X); Mao, Ying (Y); Bao, Weiming (W); Gao, Liang (L); Zhou, Ping (P); Xie, Rong (R); Zhou, Liangfu (L); Zhu, Jianhong (J);

Affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neurosurgery (Neurosurgery), published in United States. (Language: eng)

Reference: 2009-Sep; vol 65 (issue 3) : pp 610-24; discussion 624

Dates: Created 2009/08/18; Completed 2009/11/04;

PMID: 19687708, status: MEDLINE (last retrieval date: 11/4/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Apoptosis - drug effects; genetics Brain Neoplasms Brain Stem Neoplasms - therapy Cell Line, Tumor Cell Movement Disease Models, Animal Genetic Engineering - methods Glioma - therapy Humans In Situ Nick-End Labeling Male

Mesenchymal Stem Cells - physiology Mice Mice, Nude Neoplasm Transplantation - methods RNA, Small Interfering - genetics; pharmacology Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics; metabolism Receptors, Tumor Necrosis Factor - genetics; metabolism TNF-Related Apoptosis-Inducing Ligand - genetics; metabolism Time Factors Transfection - methods Tumor Necrosis Factor-alpha - genetics; metabolism Xenograft Model Antitumor Assays - methods

Associated Chemicals: RNA, Small Interfering (0) ; Receptors, TNF-Related Apoptosis-Inducing Ligand (0) ; Receptors, Tumor Necrosis Factor (0) ; TNF-Related Apoptosis-Inducing Ligand (0) ; TNFRSF10A protein, human (0) ; Tumor Necrosis Factor-alpha (0)

Related articles

These are the highest related articles currently in the database:

• Pharmacological inhibition of Bcl-2 family members reactivates TRAIL-induced apoptosis in malignant glioma. 7 Oct 2007
• Upregulation of DR5 by proteasome inhibitors potently sensitizes glioma cells to TRAIL-induced apoptosis. 11 Mar 2008
• A human scFv antibody against TRAIL receptor 2 induces autophagic cell death in both TRAIL-sensitive and TRAIL-resistant cancer cells. 30 Jul 2007
• TRAIL and KILLER are expressed and induce apoptosis in the murine preimplantation embryo. 3 May 2004
• Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma. 29 Nov 2008
• Downregulation of PIK3CB by siRNA suppresses malignant glioma cell growth in vitro and in vivo. 30 May 2006
• Specific resistance upon lentiviral TRAIL transfer by intracellular retention of TRAIL receptors. 8 Feb 2006
• Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression. 29 Nov 2000
• Apoptosis signaling pathways and lymphocyte homeostasis. 30 Aug 2007
• Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide. 30 Oct 2008

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.