國家衛生研究院 NHRI:Item 3990099045/12923

NHRI > Institute of Biomedical Engineering and Nanomedicine > Chung-Shi Yang > Periodical Articles > Item 3990099045/12923

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12923

Title:	A doxycycline-inducible C17.2 neural stem cell-based combination of differentiation and suicide gene therapy for anin vitrotumorigenic C6 glioma model
Authors:	Chu, IR;Pan, RL;Yang, CS;Wu, LC
Contributors:	Institute of Biomedical Engineering and Nanomedicine
Abstract:	Neural stem cell (NSC)-based gene therapies have been recently developed as effective strategies for treating brain tumors through inherent tumor tropism. However, this methodology has two considerable challenges: preventing NSCs from dying from the therapeutic agents encoded by their equipped genes before reaching tumor sites and the clearance of exogenous NSCs after therapeutic treatments. For these purposes, we established a novel doxycycline-inducible retroviral plasmid pTRE3G-TKGFP. A herpes simplex type 1 thymidine kinase (HSV1TK)-green fluorescent protein (GFP) fusion protein coding sequence was integrated into the multiple cloning site II (MCS II) of the pQcXIX vector, and the CMV IE promoter (P-CMV IE) of pQcXIX was replaced with the doxycycline-inducible TRE3G promoter (P-TRE3G). We then cloned the coding sequences of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and soluble interleukin 6 receptor (sIL-6R) into MCS I to combine HSV1TK (TK)/ganciclovir (GCV)-based suicide gene therapy against tumorigenic C6 glioma cells. TNF-alpha, IL-6 and sIL6R could efficiently induce tumorigenic C6 glioma cell differentiation, resulted in down-regulating the cell proliferation rate and the tumorigenicity of glioma cells and up-regulating the production of differentiation markers, such as connexin-43. Furthermore, gap junctions could enhance the bystander effect in suicide gene therapy. Consequently, we found that the retroviral plasmid transfected NSCs exerted stronger remedial effects on tumorigenic C6 glioma cells through the combination of differentiation and suicide gene therapy than by suicide gene therapy alone. This study is also the first case applying NSCs to conduct the combination of differentiation and TK/GCV-based suicide gene therapy on glioma cells.
Date:	2020-01
Relation:	Biotechnology and Biotechnological Equipment. 2020 Jan;34(1):986-998.
Link to:	http://dx.doi.org/10.1080/13102818.2020.1804449
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1310-2818&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000565344100001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85090114232
Appears in Collections:	[Chung-Shi Yang] Periodical Articles

Files in This Item:

File	Description	Size	Format
ISI000565344100001.pdf		2908Kb	Adobe PDF	261	View/Open

Loading...