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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Auteurs principaux:	Ekaterina S. Zubkova, Irina B. Beloglazova, Elizaveta I. Ratner, Daniyar T. Dyikanov, Konstantin V. Dergilev, Mikhail Yu. Menshikov, Yelena V. Parfyonova
Format:	article
Langue:	EN
Publié:	The Company of Biologists 2021
Sujets:	adeno-associated viral vectors gene therapy mesenchymal stromal cells Science Q Biology (General) QH301-705.5
Accès en ligne:	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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Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ

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