AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study

<p>Abstract</p> <p>Background</p> <p>Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (...

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Main Authors: Knight Robert A, Janic Branislava, Iskander ASM, Rad Ali M, Arbab Ali S, Soltanian-Zadeh Hamid
Format: Article
Language:English
Published: BMC 2009-03-01
Series:BMC Biotechnology
Online Access:http://www.biomedcentral.com/1472-6750/9/28
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spelling doaj-d7be11759e824ed9b223428fa0454c752020-11-25T03:40:02ZengBMCBMC Biotechnology1472-67502009-03-01912810.1186/1472-6750-9-28AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary studyKnight Robert AJanic BranislavaIskander ASMRad Ali MArbab Ali SSoltanian-Zadeh Hamid<p>Abstract</p> <p>Background</p> <p>Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC) can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI). In this study, we used superparamagentic iron oxide (SPIO)-labeled APCs to carry the human sodium iodide symporter (hNIS) gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m) scan.</p> <p>Results</p> <p>Three million human breast cancer (MDA-MB-231) cells were subcutaneously implanted in the right flank of nude mice. APCs, isolated from fresh human cord blood, were genetically transformed to carry the hNIS gene using adenoviral vectors and magnetically labeled with ferumoxides-protamine sulfate (FePro) complexes. Magnetically labeled genetically transformed cells were administered intravenously in tumor bearing mice when tumors reached 0.5 cm in the largest dimension. MRI and single photon emission computed tomography (SPECT) images were acquired 3 and 7 days after cell injection, with a 7 Tesla animal MRI system and a custom built micro-SPECT using Tc-99m, respectively. Expression of hNIS in accumulated cells was determined by staining with anti-hNIS antibody. APCs were efficiently labeled with ferumoxide-protamine sulfate (FePro) complexes and transduced with hNIS gene. Our study showed not only the accumulation of intravenously administered genetically transformed, magnetically labeled APCs in the implanted breast cancer, but also the expression of hNIS gene at the tumor site. Tc-99m activity ratio (tumor/non-tumor) was significantly different between animals that received non-transduced and transduced cells (P < 0.001).</p> <p>Conclusion</p> <p>This study indicates that genetically transformed, magnetically labeled APCs can be used both as delivery vehicles and cellular probes for detecting <it>in vivo </it>migration and homing of cells. Furthermore, they can potentially be used as a gene carrier system for the treatment of tumor or other diseases.</p> http://www.biomedcentral.com/1472-6750/9/28
collection DOAJ
language English
format Article
sources DOAJ
author Knight Robert A
Janic Branislava
Iskander ASM
Rad Ali M
Arbab Ali S
Soltanian-Zadeh Hamid
spellingShingle Knight Robert A
Janic Branislava
Iskander ASM
Rad Ali M
Arbab Ali S
Soltanian-Zadeh Hamid
AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study
BMC Biotechnology
author_facet Knight Robert A
Janic Branislava
Iskander ASM
Rad Ali M
Arbab Ali S
Soltanian-Zadeh Hamid
author_sort Knight Robert A
title AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study
title_short AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study
title_full AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study
title_fullStr AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study
title_full_unstemmed AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study
title_sort ac133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study
publisher BMC
series BMC Biotechnology
issn 1472-6750
publishDate 2009-03-01
description <p>Abstract</p> <p>Background</p> <p>Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC) can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI). In this study, we used superparamagentic iron oxide (SPIO)-labeled APCs to carry the human sodium iodide symporter (hNIS) gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m) scan.</p> <p>Results</p> <p>Three million human breast cancer (MDA-MB-231) cells were subcutaneously implanted in the right flank of nude mice. APCs, isolated from fresh human cord blood, were genetically transformed to carry the hNIS gene using adenoviral vectors and magnetically labeled with ferumoxides-protamine sulfate (FePro) complexes. Magnetically labeled genetically transformed cells were administered intravenously in tumor bearing mice when tumors reached 0.5 cm in the largest dimension. MRI and single photon emission computed tomography (SPECT) images were acquired 3 and 7 days after cell injection, with a 7 Tesla animal MRI system and a custom built micro-SPECT using Tc-99m, respectively. Expression of hNIS in accumulated cells was determined by staining with anti-hNIS antibody. APCs were efficiently labeled with ferumoxide-protamine sulfate (FePro) complexes and transduced with hNIS gene. Our study showed not only the accumulation of intravenously administered genetically transformed, magnetically labeled APCs in the implanted breast cancer, but also the expression of hNIS gene at the tumor site. Tc-99m activity ratio (tumor/non-tumor) was significantly different between animals that received non-transduced and transduced cells (P < 0.001).</p> <p>Conclusion</p> <p>This study indicates that genetically transformed, magnetically labeled APCs can be used both as delivery vehicles and cellular probes for detecting <it>in vivo </it>migration and homing of cells. Furthermore, they can potentially be used as a gene carrier system for the treatment of tumor or other diseases.</p>
url http://www.biomedcentral.com/1472-6750/9/28
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