GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS

Abstract Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease. CD68-positive bone marrow (BM)-derived cells (BMDCs) accumulate in the pathological lesion in the SOD1(G93A) ALS mouse model after BM transplantation (BMT). Therefore, we investigated whether BMDCs can be appli...

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Autores principales:	Natsuko Ohashi, Tomoya Terashima, Miwako Katagi, Yuki Nakae, Junko Okano, Yoshihisa Suzuki, Hideto Kojima
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54be9e626a714971ae9b84bc8055e8a3
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spelling	oai:doaj.org-article:54be9e626a714971ae9b84bc8055e8a32021-12-02T17:41:10ZGLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS10.1038/s41598-021-92285-x2045-2322https://doaj.org/article/54be9e626a714971ae9b84bc8055e8a32021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92285-xhttps://doaj.org/toc/2045-2322Abstract Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease. CD68-positive bone marrow (BM)-derived cells (BMDCs) accumulate in the pathological lesion in the SOD1(G93A) ALS mouse model after BM transplantation (BMT). Therefore, we investigated whether BMDCs can be applied as gene carriers for cell-based gene therapy by employing the accumulation of BMDCs. In ALS mice, YFP reporter signals were observed in 12–14% of white blood cells (WBCs) and in the spinal cord via transplantation of BM after lentiviral vector (LV) infection. After confirmation of gene transduction by LV with the CD68 promoter in 4–7% of WBCs and in the spinal cord of ALS mice, BM cells were infected with LVs expressing glutamate transporter (GLT) 1 that protects neurons from glutamate toxicity, driven by the CD68 promoter, which were transplanted into ALS mice. The treated mice showed improvement of motor behaviors and prolonged survival. Additionally, interleukin (IL)-1β was significantly suppressed, and IL-4, arginase 1, and FIZZ were significantly increased in the mice. These results suggested that GLT1 expression by BMDCs improved the spinal cord environment. Therefore, our gene therapy strategy may be applied to treat neurodegenerative diseases such as ALS in which BMDCs accumulate in the pathological lesion by BMT.Natsuko OhashiTomoya TerashimaMiwako KatagiYuki NakaeJunko OkanoYoshihisa SuzukiHideto KojimaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natsuko Ohashi Tomoya Terashima Miwako Katagi Yuki Nakae Junko Okano Yoshihisa Suzuki Hideto Kojima GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS
description	Abstract Amyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease. CD68-positive bone marrow (BM)-derived cells (BMDCs) accumulate in the pathological lesion in the SOD1(G93A) ALS mouse model after BM transplantation (BMT). Therefore, we investigated whether BMDCs can be applied as gene carriers for cell-based gene therapy by employing the accumulation of BMDCs. In ALS mice, YFP reporter signals were observed in 12–14% of white blood cells (WBCs) and in the spinal cord via transplantation of BM after lentiviral vector (LV) infection. After confirmation of gene transduction by LV with the CD68 promoter in 4–7% of WBCs and in the spinal cord of ALS mice, BM cells were infected with LVs expressing glutamate transporter (GLT) 1 that protects neurons from glutamate toxicity, driven by the CD68 promoter, which were transplanted into ALS mice. The treated mice showed improvement of motor behaviors and prolonged survival. Additionally, interleukin (IL)-1β was significantly suppressed, and IL-4, arginase 1, and FIZZ were significantly increased in the mice. These results suggested that GLT1 expression by BMDCs improved the spinal cord environment. Therefore, our gene therapy strategy may be applied to treat neurodegenerative diseases such as ALS in which BMDCs accumulate in the pathological lesion by BMT.
format	article
author	Natsuko Ohashi Tomoya Terashima Miwako Katagi Yuki Nakae Junko Okano Yoshihisa Suzuki Hideto Kojima
author_facet	Natsuko Ohashi Tomoya Terashima Miwako Katagi Yuki Nakae Junko Okano Yoshihisa Suzuki Hideto Kojima
author_sort	Natsuko Ohashi
title	GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS
title_short	GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS
title_full	GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS
title_fullStr	GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS
title_full_unstemmed	GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS
title_sort	glt1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of als
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/54be9e626a714971ae9b84bc8055e8a3
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GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS

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