Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation

Wada, Miho; Shimada, Yohta; Iizuka, Sayoko; Ishii, Natsumi; Hiraki, Hiromi; Tachibana, Toshiaki; Maeda, Kazuhiro; Saito, Mitsuru; Arakawa, Shoutaro; Ishimoto, Takuya; Nakano, Takayoshi; Ida, Hiroyuki; Ohashi, Toya; Kobayashi, Hiroshi

doi:https://doi.org/10.1016/j.omtm.2020.09.012

Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation

Wada, Miho; Shimada, Yohta; Iizuka, Sayoko et al.

Molecular Therapy - Methods and Clinical Development, 2020, 19, 261-274

Number of Access:1,378（2025-07-18 10:08 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/89796

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Title	Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation
Creator	CreatorName Wada, Miho
	NRID 1000020560824 1000020560824 CreatorName Shimada, Yohta
	CreatorName Iizuka, Sayoko
	CreatorName Ishii, Natsumi
	CreatorName Hiraki, Hiromi
	NRID 1000080163476 1000080163476 CreatorName Tachibana, Toshiaki
	NRID 1000050548849 1000050548849 CreatorName Maeda, Kazuhiro
	NRID 1000050301528 1000050301528 CreatorName Saito, Mitsuru
	CreatorName Arakawa, Shoutaro
	NRID 1000050508835 1000050508835 ORCID 0000-0003-0081-0591 0000-0003-0081-0591 researchmap permalink i_taku i_taku Scopus Author ID 35310484700 35310484700 CreatorName Ishimoto, Takuya
	NRID 1000030243182 1000030243182 ORCID 0000-0001-8052-1698 0000-0001-8052-1698 researchmap permalink read0013987 read0013987 Scopus Author ID 7403896013 7403896013 CreatorName Nakano, Takayoshi
	NRID 1000090167255 1000090167255 CreatorName Ida, Hiroyuki
	CreatorName Ohashi, Toya
	NRID 1000010570814 1000010570814 CreatorName Kobayashi, Hiroshi
Subject	bone lineage
	bone mineral density
	bone strength
	ex vivo gene therapy
	hematopoietic stem cell
	Hunter disease
	lentivirus
	mucopolysaccharidosis type II
	osteoblast
	osteoclast
Description	Wada M., Shimada Y., Iizuka S., et al. Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation. Molecular Therapy - Methods and Clinical Development, 19, 261. https://doi.org/10.1016/j.omtm.2020.09.012.
Abstract	Mucopolysaccharidosis type II is a disease caused by organ accumulation of glycosaminoglycans due to iduronate 2-sulfatase deficiency. This study investigated the pathophysiology of the bone complications associated with mucopolysaccharidosis II and the effect of lentivirus-mediated gene therapy of hematopoietic stem cells on bone lesions of mucopolysaccharidosis type II mouse models in comparison with enzyme replacement therapy. Bone volume, density, strength, and trabecular number were significantly higher in the untreated mucopolysaccharidosis type II mice than in wild-type mice. Accumulation of glycosaminoglycans caused reduced bone metabolism. Specifically, persistent high serum iduronate 2-sulfatase levels and release of glycosaminoglycans from osteoblasts and osteoclasts in mucopolysaccharidosis type II mice that had undergone gene therapy reactivated bone lineage remodeling, subsequently reducing bone mineral density, strength, and trabecular number to a similar degree as that observed in wild-type mice. Bone formation, resorption parameters, and mineral density in the diaphysis edge did not appear to have been affected by the irradiation administered as a pre-treatment for gene therapy. Hence, the therapeutic effect of gene therapy on the bone complications of mucopolysaccharidosis type II mice possibly outweighed that of enzyme replacement therapy in many aspects.
Publisher	Cell Press
Source Title	Molecular Therapy - Methods and Clinical Development
Volume (Issue)	19
Page	261-274
Date of Issued	2020-12-11
Language	English
Handle URL	https://hdl.handle.net/11094/89796
eISSN	23290501
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.omtm.2020.09.012
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Molecular Therapy - Methods and Clinical Development. 2020, 19, p. 261-274
DC.title	Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation
DC.creator	Wada, Miho
	Shimada, Yohta
	Iizuka, Sayoko
	Ishii, Natsumi
	Hiraki, Hiromi
	Tachibana, Toshiaki
	Maeda, Kazuhiro
	Saito, Mitsuru
	Arakawa, Shoutaro
	Ishimoto, Takuya
	Nakano, Takayoshi
	Ida, Hiroyuki
	Ohashi, Toya
	Kobayashi, Hiroshi
DC.publisher	Cell Press
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-12-11
DC.identifier	https://doi.org/10.1016/j.omtm.2020.09.012
DC.subject	bone lineage
	bone mineral density
	bone strength
	ex vivo gene therapy
	hematopoietic stem cell
	Hunter disease
	lentivirus
	mucopolysaccharidosis type II
	osteoblast
	osteoclast
DC.description	Wada M., Shimada Y., Iizuka S., et al. Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation. Molecular Therapy - Methods and Clinical Development, 19, 261. https://doi.org/10.1016/j.omtm.2020.09.012.
DCTERMS.abstract	Mucopolysaccharidosis type II is a disease caused by organ accumulation of glycosaminoglycans due to iduronate 2-sulfatase deficiency. This study investigated the pathophysiology of the bone complications associated with mucopolysaccharidosis II and the effect of lentivirus-mediated gene therapy of hematopoietic stem cells on bone lesions of mucopolysaccharidosis type II mouse models in comparison with enzyme replacement therapy. Bone volume, density, strength, and trabecular number were significantly higher in the untreated mucopolysaccharidosis type II mice than in wild-type mice. Accumulation of glycosaminoglycans caused reduced bone metabolism. Specifically, persistent high serum iduronate 2-sulfatase levels and release of glycosaminoglycans from osteoblasts and osteoclasts in mucopolysaccharidosis type II mice that had undergone gene therapy reactivated bone lineage remodeling, subsequently reducing bone mineral density, strength, and trabecular number to a similar degree as that observed in wild-type mice. Bone formation, resorption parameters, and mineral density in the diaphysis edge did not appear to have been affected by the irradiation administered as a pre-treatment for gene therapy. Hence, the therapeutic effect of gene therapy on the bone complications of mucopolysaccharidosis type II mice possibly outweighed that of enzyme replacement therapy in many aspects.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	89796
citation_title	Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation
citation_author	Wada, Miho
	Shimada, Yohta
	Iizuka, Sayoko
	Ishii, Natsumi
	Hiraki, Hiromi
	Tachibana, Toshiaki
	Maeda, Kazuhiro
	Saito, Mitsuru
	Arakawa, Shoutaro
	Ishimoto, Takuya
	Nakano, Takayoshi
	Ida, Hiroyuki
	Ohashi, Toya
	Kobayashi, Hiroshi
citation_publisher	Cell Press
citation_language	English
citation_date	2020-12-11
citation_journal_title	Molecular Therapy - Methods and Clinical Development
citation_volume	19
citation_firstpage	261
citation_lastpage	274
citation_doi	https://doi.org/10.1016/j.omtm.2020.09.012
citation_public_url	https://hdl.handle.net/11094/89796

Ex Vivo Gene Therapy Treats Bone Complications of Mucopolysaccharidosis Type II Mouse Models through Bone Remodeling Reactivation

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