Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+ hMSCs

Genetic modifications of bone marrow derived human mesenchymal stem cells (hMSCs) using microRNAs (miRs) may be used to improve their therapeutic potential and enable innovative strategies in tissue regeneration. However, most of the studies use cultured hMSCs, although these can lose their stem cel...

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Main Authors: Anna Schade, Paula Müller, Evgenya Delyagina, Natalia Voronina, Anna Skorska, Cornelia Lux, Gustav Steinhoff, Robert David
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2014/197154
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author Anna Schade
Paula Müller
Evgenya Delyagina
Natalia Voronina
Anna Skorska
Cornelia Lux
Gustav Steinhoff
Robert David
author_facet Anna Schade
Paula Müller
Evgenya Delyagina
Natalia Voronina
Anna Skorska
Cornelia Lux
Gustav Steinhoff
Robert David
author_sort Anna Schade
collection DOAJ
description Genetic modifications of bone marrow derived human mesenchymal stem cells (hMSCs) using microRNAs (miRs) may be used to improve their therapeutic potential and enable innovative strategies in tissue regeneration. However, most of the studies use cultured hMSCs, although these can lose their stem cell characteristics during expansion. Therefore, we aimed to develop a nonviral miR carrier based on polyethylenimine (PEI) bound to magnetic nanoparticles (MNPs) for efficient miR delivery in freshly isolated hMSCs. MNP based transfection is preferable for genetic modifications in vivo due to improved selectivity, safety of delivery, and reduced side effects. Thus, in this study different miR/PEI and miR/PEI/MNP complex formulations were tested in vitro for uptake efficiency and cytotoxicity with respect to the influence of an external magnetic field. Afterwards, optimized magnetic complexes were selected and compared to commercially available magnetic vectors (Magnetofectamine, CombiMag). We found that all tested transfection reagents had high miR uptake rates (yielded over 60%) and no significant cytotoxic effects. Our work may become crucial for virus-free introduction of therapeutic miRs as well as other nucleic acids in vivo. Moreover, in the field of targeted stem cell therapy nucleic acid delivery prior to transplantation may allowfor initial cell modulation in vitro.
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spelling doaj-art-1971ce4843e64eddb2d1a39ed8ca6b612025-02-03T06:07:01ZengWileyStem Cells International1687-966X1687-96782014-01-01201410.1155/2014/197154197154Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+ hMSCsAnna Schade0Paula Müller1Evgenya Delyagina2Natalia Voronina3Anna Skorska4Cornelia Lux5Gustav Steinhoff6Robert David7Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 35, 18057 Rostock, GermanyDepartment of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 35, 18057 Rostock, GermanyGenetic modifications of bone marrow derived human mesenchymal stem cells (hMSCs) using microRNAs (miRs) may be used to improve their therapeutic potential and enable innovative strategies in tissue regeneration. However, most of the studies use cultured hMSCs, although these can lose their stem cell characteristics during expansion. Therefore, we aimed to develop a nonviral miR carrier based on polyethylenimine (PEI) bound to magnetic nanoparticles (MNPs) for efficient miR delivery in freshly isolated hMSCs. MNP based transfection is preferable for genetic modifications in vivo due to improved selectivity, safety of delivery, and reduced side effects. Thus, in this study different miR/PEI and miR/PEI/MNP complex formulations were tested in vitro for uptake efficiency and cytotoxicity with respect to the influence of an external magnetic field. Afterwards, optimized magnetic complexes were selected and compared to commercially available magnetic vectors (Magnetofectamine, CombiMag). We found that all tested transfection reagents had high miR uptake rates (yielded over 60%) and no significant cytotoxic effects. Our work may become crucial for virus-free introduction of therapeutic miRs as well as other nucleic acids in vivo. Moreover, in the field of targeted stem cell therapy nucleic acid delivery prior to transplantation may allowfor initial cell modulation in vitro.http://dx.doi.org/10.1155/2014/197154
spellingShingle Anna Schade
Paula Müller
Evgenya Delyagina
Natalia Voronina
Anna Skorska
Cornelia Lux
Gustav Steinhoff
Robert David
Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+ hMSCs
Stem Cells International
title Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+ hMSCs
title_full Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+ hMSCs
title_fullStr Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+ hMSCs
title_full_unstemmed Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+ hMSCs
title_short Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+ hMSCs
title_sort magnetic nanoparticle based nonviral microrna delivery into freshly isolated cd105 hmscs
url http://dx.doi.org/10.1155/2014/197154
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