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E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice

Gene therapy is an attractive approach for hepatocellular carcinoma (HCC) patients. Nevertheless, efficient transgene delivery remains a challenge. In this study, we explored a new targeted system based on human umbilical cord-derived mesenchymal stem cells (HUMSCs), which were engineered to deliver...

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Autores principales: Li, Zhenzhen, Ye, Zhou, Zhang, Xiaolong, Zhang, Qing, Fan, Dongmei, Zhang, Yanjun, Luo, Hongbo R., Yuan, Xiangfei, Li, Zongfang, Xiong, Dongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239516/
https://www.ncbi.nlm.nih.gov/pubmed/27322080
http://dx.doi.org/10.18632/oncotarget.10122
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author Li, Zhenzhen
Ye, Zhou
Zhang, Xiaolong
Zhang, Qing
Fan, Dongmei
Zhang, Yanjun
Luo, Hongbo R.
Yuan, Xiangfei
Li, Zongfang
Xiong, Dongsheng
author_facet Li, Zhenzhen
Ye, Zhou
Zhang, Xiaolong
Zhang, Qing
Fan, Dongmei
Zhang, Yanjun
Luo, Hongbo R.
Yuan, Xiangfei
Li, Zongfang
Xiong, Dongsheng
author_sort Li, Zhenzhen
collection PubMed
description Gene therapy is an attractive approach for hepatocellular carcinoma (HCC) patients. Nevertheless, efficient transgene delivery remains a challenge. In this study, we explored a new targeted system based on human umbilical cord-derived mesenchymal stem cells (HUMSCs), which were engineered to deliver adenovirus to tumor sites, and to replicate and assemble into new adenovirus against HCC. Our results showed that HUMSCs infected by Ad-hTERTp-IL24 followed by LentiR.E1A infection could specifically migrate to HepG2 tumor cells and support adenoviral replication in vitro and in vivo 36 h after LentiR.E1A infection. Ad-hTERTp-IL24 specifically inhibited HepG2 cells growth, and this inhibitory effect was enhanced by low doses of 5-fluorouracil (5-Fu), because the expression levels of coxsackie adenovirus receptor (CAR) and integrin ανβ3 on tumor cells were significantly increased, causing higher viral uptake. Compared with the no treatment groups, Ad-hTERTp-IL24 and LentiR.E1A co-loaded HUMSCs exhibited significant anti-tumor activity in vivo, particularly in combination with low doses of 5-Fu. In summary, this study provides a promising targeted gene therapeutic strategy dependent on the tumor tropism of HUMSCs, to improve the outcome of virotherapy for tumor patients especially those with metastatic diseases.
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spelling pubmed-52395162017-01-24 E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice Li, Zhenzhen Ye, Zhou Zhang, Xiaolong Zhang, Qing Fan, Dongmei Zhang, Yanjun Luo, Hongbo R. Yuan, Xiangfei Li, Zongfang Xiong, Dongsheng Oncotarget Research Paper Gene therapy is an attractive approach for hepatocellular carcinoma (HCC) patients. Nevertheless, efficient transgene delivery remains a challenge. In this study, we explored a new targeted system based on human umbilical cord-derived mesenchymal stem cells (HUMSCs), which were engineered to deliver adenovirus to tumor sites, and to replicate and assemble into new adenovirus against HCC. Our results showed that HUMSCs infected by Ad-hTERTp-IL24 followed by LentiR.E1A infection could specifically migrate to HepG2 tumor cells and support adenoviral replication in vitro and in vivo 36 h after LentiR.E1A infection. Ad-hTERTp-IL24 specifically inhibited HepG2 cells growth, and this inhibitory effect was enhanced by low doses of 5-fluorouracil (5-Fu), because the expression levels of coxsackie adenovirus receptor (CAR) and integrin ανβ3 on tumor cells were significantly increased, causing higher viral uptake. Compared with the no treatment groups, Ad-hTERTp-IL24 and LentiR.E1A co-loaded HUMSCs exhibited significant anti-tumor activity in vivo, particularly in combination with low doses of 5-Fu. In summary, this study provides a promising targeted gene therapeutic strategy dependent on the tumor tropism of HUMSCs, to improve the outcome of virotherapy for tumor patients especially those with metastatic diseases. Impact Journals LLC 2016-06-17 /pmc/articles/PMC5239516/ /pubmed/27322080 http://dx.doi.org/10.18632/oncotarget.10122 Text en Copyright: © 2016 Li et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Li, Zhenzhen
Ye, Zhou
Zhang, Xiaolong
Zhang, Qing
Fan, Dongmei
Zhang, Yanjun
Luo, Hongbo R.
Yuan, Xiangfei
Li, Zongfang
Xiong, Dongsheng
E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice
title E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice
title_full E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice
title_fullStr E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice
title_full_unstemmed E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice
title_short E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice
title_sort e1a-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5239516/
https://www.ncbi.nlm.nih.gov/pubmed/27322080
http://dx.doi.org/10.18632/oncotarget.10122
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