Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and <it>in vivo </it>visualization by magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate <it>in vivo</it>...

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Main Authors: Spray David C, Gasparetto Emerson L, Jelicks Linda A, Passipieri Juliana A, Nunes Henrique MP, Torres Ana Luiza M, Jasmin, Campos de Carvalho Antonio C, Mendez-Otero Rosalia
Format: Article
Language:English
Published: BMC 2011-02-01
Series:Journal of Nanobiotechnology
Online Access:http://www.jnanobiotechnology.com/content/9/1/4
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author Spray David C
Gasparetto Emerson L
Jelicks Linda A
Passipieri Juliana A
Nunes Henrique MP
Torres Ana Luiza M
Jasmin
Campos de Carvalho Antonio C
Mendez-Otero Rosalia
author_facet Spray David C
Gasparetto Emerson L
Jelicks Linda A
Passipieri Juliana A
Nunes Henrique MP
Torres Ana Luiza M
Jasmin
Campos de Carvalho Antonio C
Mendez-Otero Rosalia
author_sort Spray David C
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate <it>in vivo</it>. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs.</p> <p>Results</p> <p>Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated <it>in vitro </it>with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells.</p> <p>Conclusions</p> <p>The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use.</p>
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spelling doaj.art-23353adae6134f37988a9fe66a4d5d212022-12-22T04:22:01ZengBMCJournal of Nanobiotechnology1477-31552011-02-0191410.1186/1477-3155-9-4Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and <it>in vivo </it>visualization by magnetic resonance imagingSpray David CGasparetto Emerson LJelicks Linda APassipieri Juliana ANunes Henrique MPTorres Ana Luiza MJasminCampos de Carvalho Antonio CMendez-Otero Rosalia<p>Abstract</p> <p>Background</p> <p>Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate <it>in vivo</it>. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs.</p> <p>Results</p> <p>Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated <it>in vitro </it>with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells.</p> <p>Conclusions</p> <p>The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use.</p>http://www.jnanobiotechnology.com/content/9/1/4
spellingShingle Spray David C
Gasparetto Emerson L
Jelicks Linda A
Passipieri Juliana A
Nunes Henrique MP
Torres Ana Luiza M
Jasmin
Campos de Carvalho Antonio C
Mendez-Otero Rosalia
Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and <it>in vivo </it>visualization by magnetic resonance imaging
Journal of Nanobiotechnology
title Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and <it>in vivo </it>visualization by magnetic resonance imaging
title_full Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and <it>in vivo </it>visualization by magnetic resonance imaging
title_fullStr Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and <it>in vivo </it>visualization by magnetic resonance imaging
title_full_unstemmed Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and <it>in vivo </it>visualization by magnetic resonance imaging
title_short Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and <it>in vivo </it>visualization by magnetic resonance imaging
title_sort optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and it in vivo it visualization by magnetic resonance imaging
url http://www.jnanobiotechnology.com/content/9/1/4
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