Bcl-2 Overexpression Improves Survival and Efficacy of Neural Stem Cell-Mediated Enzyme Prodrug Therapy.

Stem Cells International
Rachael MooneyKaren S Aboody

Abstract

Tumor-tropic neural stem cells (NSCs) can be engineered to localize gene therapies to invasive brain tumors. However, like other stem cell-based therapies, survival of therapeutic NSCs after transplantation is currently suboptimal. One approach to prolonging cell survival is to transiently overexpress an antiapoptotic protein within the cells prior to transplantation. Here, we investigate the utility and safety of this approach using a clinically tested, v-myc immortalized, human NSC line engineered to contain the suicide gene, cytosine deaminase (CD-NSCs). We demonstrate that both adenoviral- and minicircle-driven expression of the antiapoptotic protein Bcl-2 can partially rescue CD-NSCs from transplant-associated insults. We further demonstrate that the improved CD-NSC survival afforded by transient Bcl-2 overexpression results in decreased tumor burden in an orthotopic xenograft glioma mouse model following administrations of intracerebral CD-NSCs and systemic prodrug. Importantly, no evidence of CD-NSC transformation was observed upon transient overexpression of Bcl-2. This research highlights a critical need to develop clinically relevant strategies to improve survival of therapeutic stem cell posttransplantation. We demon...Continue Reading

References

Oct 1, 1995·The Journal of Pathology·S X JiangT Kameya
Oct 22, 1993·Cell·D M HockenberyS J Korsmeyer
Jun 11, 1999·Journal of Virology·A HaruiK Mitani
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·K S AboodyE Y Snyder
May 27, 2004·Biotechnology and Bioengineering·Jolene M Ignowski, David V Schaffer
Aug 5, 2005·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·M-A MicciP J Pasricha
May 5, 2007·Stem Cells·Wenzhong LiGustav Steinhoff
Jan 12, 2008·Cancer Gene Therapy·M WierdlP M Potter
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Reza ArdehaliIrving L Weissman
May 10, 2013·Science Translational Medicine·Karen S AboodyJana Portnow
Aug 13, 2013·Stem Cells Translational Medicine·Jeong HyunMichael T Longaker
Dec 17, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jana PortnowKaren S Aboody

❮ Previous
Next ❯

Citations

Aug 23, 2018·Stem Cells Translational Medicine·Rachael MooneyKaren S Aboody
Mar 24, 2021·Cancer Gene Therapy·Aparna Ramanathan, Ian A J Lorimer
Jun 18, 2021·World Journal of Stem Cells·Xi-Min HuKun Xiong

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
transgenic
transfection
Flow
xenografts
confocal microscopy
xenograft
flow cytometry
electrophoresis
Knockdown

Clinical Trials Mentioned

NCT01172964
NCT02015819
NCT02192359

Software Mentioned

MassLynx
FlowJo
ImageJ
Living Image

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Related Papers

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Do-Hun LeeSeung-Ki Kim
Molecular Therapy : the Journal of the American Society of Gene Therapy
Kyeung Min JooDo-Hyun Nam
© 2022 Meta ULC. All rights reserved