Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ

Ex vivo, gene therapy is a powerful approach holding great promises for the treatment of both genetic and acquired diseases. Adeno-associated virus (AAV) vectors are a safe and efficient delivery system for modification of mesenchymal stem cells (MSC) that could maximize their therapeutic benefits....

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Autores principales: Ekaterina S. Zubkova, Irina B. Beloglazova, Elizaveta I. Ratner, Daniyar T. Dyikanov, Konstantin V. Dergilev, Mikhail Yu. Menshikov, Yelena V. Parfyonova
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Lenguaje:EN
Publicado: The Company of Biologists 2021
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Acceso en línea:https://doaj.org/article/abd2febe167b47d491a73cfaa1c924e5
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spelling oai:doaj.org-article:abd2febe167b47d491a73cfaa1c924e52021-11-28T16:01:04ZTransduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ2046-639010.1242/bio.058461https://doaj.org/article/abd2febe167b47d491a73cfaa1c924e52021-09-01T00:00:00Zhttp://bio.biologists.org/content/10/9/bio058461https://doaj.org/toc/2046-6390Ex vivo, gene therapy is a powerful approach holding great promises for the treatment of both genetic and acquired diseases. Adeno-associated virus (AAV) vectors are a safe and efficient delivery system for modification of mesenchymal stem cells (MSC) that could maximize their therapeutic benefits. Assessment of MSC viability and functional activity after infection with new AAV serotypes is necessary, due to AAV tropism to specific cell types. We infected human and rat adipose-tissue MSC with hybrid AAV-DJ serotype vectors carrying GFP and SCF genes. GFP expression from AAV-DJ was about 1.5-fold superior to that observed with AAV-2 and lasted for at least 21 days as was evaluated by flow cytometry and fluorescence microscopy. AAV-DJ proves to be suitable for the infection of rat and human MSC with a similar efficiency. Infected MSC were still viable but showed a 25-30% growth-rate slowdown. Moreover, we found an increase of SERPINB2 mRNA expression in human MSC while expression of other oxidative stress markers and extracellular matrix proteins was not affected. These results suggest that there is a differential cellular response in MSC infected with AAV viral vectors, which should be taken into account as it can affect the expected outcome for the therapeutic application.Ekaterina S. ZubkovaIrina B. BeloglazovaElizaveta I. RatnerDaniyar T. DyikanovKonstantin V. DergilevMikhail Yu. MenshikovYelena V. ParfyonovaThe Company of Biologistsarticleadeno-associated viral vectorsgene therapymesenchymal stromal cellsScienceQBiology (General)QH301-705.5ENBiology Open, Vol 10, Iss 9 (2021)
institution DOAJ
collection DOAJ
language EN
topic adeno-associated viral vectors
gene therapy
mesenchymal stromal cells
Science
Q
Biology (General)
QH301-705.5
spellingShingle adeno-associated viral vectors
gene therapy
mesenchymal stromal cells
Science
Q
Biology (General)
QH301-705.5
Ekaterina S. Zubkova
Irina B. Beloglazova
Elizaveta I. Ratner
Daniyar T. Dyikanov
Konstantin V. Dergilev
Mikhail Yu. Menshikov
Yelena V. Parfyonova
Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ
description Ex vivo, gene therapy is a powerful approach holding great promises for the treatment of both genetic and acquired diseases. Adeno-associated virus (AAV) vectors are a safe and efficient delivery system for modification of mesenchymal stem cells (MSC) that could maximize their therapeutic benefits. Assessment of MSC viability and functional activity after infection with new AAV serotypes is necessary, due to AAV tropism to specific cell types. We infected human and rat adipose-tissue MSC with hybrid AAV-DJ serotype vectors carrying GFP and SCF genes. GFP expression from AAV-DJ was about 1.5-fold superior to that observed with AAV-2 and lasted for at least 21 days as was evaluated by flow cytometry and fluorescence microscopy. AAV-DJ proves to be suitable for the infection of rat and human MSC with a similar efficiency. Infected MSC were still viable but showed a 25-30% growth-rate slowdown. Moreover, we found an increase of SERPINB2 mRNA expression in human MSC while expression of other oxidative stress markers and extracellular matrix proteins was not affected. These results suggest that there is a differential cellular response in MSC infected with AAV viral vectors, which should be taken into account as it can affect the expected outcome for the therapeutic application.
format article
author Ekaterina S. Zubkova
Irina B. Beloglazova
Elizaveta I. Ratner
Daniyar T. Dyikanov
Konstantin V. Dergilev
Mikhail Yu. Menshikov
Yelena V. Parfyonova
author_facet Ekaterina S. Zubkova
Irina B. Beloglazova
Elizaveta I. Ratner
Daniyar T. Dyikanov
Konstantin V. Dergilev
Mikhail Yu. Menshikov
Yelena V. Parfyonova
author_sort Ekaterina S. Zubkova
title Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ
title_short Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ
title_full Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ
title_fullStr Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ
title_full_unstemmed Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ
title_sort transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype dj
publisher The Company of Biologists
publishDate 2021
url https://doaj.org/article/abd2febe167b47d491a73cfaa1c924e5
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