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BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro

The use of neurotrophic factors as therapeutic agents for neurodegenerative diseases is considered as an approach aimed at restoring and maintaining neuronal function in the peripheral and central nervous system. Since the neuroprotective effect is depending on chronic delivery of the neurotrophic f...

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Autores principales: Scheper, Verena, Schwieger, Jana, Hamm, Anika, Lenarz, Thomas, Hoffmann, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772136/
https://www.ncbi.nlm.nih.gov/pubmed/31257632
http://dx.doi.org/10.1002/jnr.24488
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author Scheper, Verena
Schwieger, Jana
Hamm, Anika
Lenarz, Thomas
Hoffmann, Andrea
author_facet Scheper, Verena
Schwieger, Jana
Hamm, Anika
Lenarz, Thomas
Hoffmann, Andrea
author_sort Scheper, Verena
collection PubMed
description The use of neurotrophic factors as therapeutic agents for neurodegenerative diseases is considered as an approach aimed at restoring and maintaining neuronal function in the peripheral and central nervous system. Since the neuroprotective effect is depending on chronic delivery of the neurotrophic factors a sustained application, e.g., via cell‐based delivery is necessary. Human mesenchymal stem cells (hMSCs) were lentivirally modified to overexpress brain‐derived neurotrophic factor (BDNF) and to express fluorescent marker genes for easy visualization. Since genetically modified cells should be site‐specifically retained (e.g., by encapsulation) in the patients to avoid adverse effects the cells were additionally differentiated to chondrocytes to hypothetically improve their vitality and survival in a delivery matrix. Different polycations for lentiviral transduction were investigated for their efficiency. The success of differentiation was determined by analysis of chondrocyte marker genes and the neuroprotective effect of BDNF‐overexpressing cells was exemplarily investigated on neurons of the peripheral auditory system. The genetically modified hMSCs overexpressed BDNF from under 1 to 125 ng ml(−1) day(−1) depending on the donor and transfection method. Using protamine sulfate the transfection efficacy was superior compared to the use of polybrene. The BDNF secreted by the MSCs was significantly neuroprotective in comparison to the relevant controls even though the produced mean concentrations were lower than the effective concentrations for recombinant industrially produced proteins described in literature. The presented system of BDNF‐overexpressing hMSCs is neuroprotective and is therefore considered as a promising method for sustained delivery of proteins in therapeutically relevant amounts to degenerating neuronal structures.
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spelling pubmed-67721362019-10-07 BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro Scheper, Verena Schwieger, Jana Hamm, Anika Lenarz, Thomas Hoffmann, Andrea J Neurosci Res Research Articles The use of neurotrophic factors as therapeutic agents for neurodegenerative diseases is considered as an approach aimed at restoring and maintaining neuronal function in the peripheral and central nervous system. Since the neuroprotective effect is depending on chronic delivery of the neurotrophic factors a sustained application, e.g., via cell‐based delivery is necessary. Human mesenchymal stem cells (hMSCs) were lentivirally modified to overexpress brain‐derived neurotrophic factor (BDNF) and to express fluorescent marker genes for easy visualization. Since genetically modified cells should be site‐specifically retained (e.g., by encapsulation) in the patients to avoid adverse effects the cells were additionally differentiated to chondrocytes to hypothetically improve their vitality and survival in a delivery matrix. Different polycations for lentiviral transduction were investigated for their efficiency. The success of differentiation was determined by analysis of chondrocyte marker genes and the neuroprotective effect of BDNF‐overexpressing cells was exemplarily investigated on neurons of the peripheral auditory system. The genetically modified hMSCs overexpressed BDNF from under 1 to 125 ng ml(−1) day(−1) depending on the donor and transfection method. Using protamine sulfate the transfection efficacy was superior compared to the use of polybrene. The BDNF secreted by the MSCs was significantly neuroprotective in comparison to the relevant controls even though the produced mean concentrations were lower than the effective concentrations for recombinant industrially produced proteins described in literature. The presented system of BDNF‐overexpressing hMSCs is neuroprotective and is therefore considered as a promising method for sustained delivery of proteins in therapeutically relevant amounts to degenerating neuronal structures. John Wiley and Sons Inc. 2019-06-30 2019-11 /pmc/articles/PMC6772136/ /pubmed/31257632 http://dx.doi.org/10.1002/jnr.24488 Text en © 2019 The Authors Journal of Neuroscience Research Published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Scheper, Verena
Schwieger, Jana
Hamm, Anika
Lenarz, Thomas
Hoffmann, Andrea
BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro
title BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro
title_full BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro
title_fullStr BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro
title_full_unstemmed BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro
title_short BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro
title_sort bdnf‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772136/
https://www.ncbi.nlm.nih.gov/pubmed/31257632
http://dx.doi.org/10.1002/jnr.24488
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