Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus

Kamatani, Takashi; Hagizawa, Hiroki; Yarimitsu, Seido; Morioka, Miho; Koyamatsu, Saeko; Sugimoto, Michihiko; Kodama, Joe; Yamane, Junko; Ishiguro, Hiroyuki; Shichino, Shigeyuki; Abe, Kuniya; Fujibuchi, Wataru; Fujie, Hiromichi; Kaito, Takashi; Tsumaki, Noriyuki

doi:https://doi.org/10.1016/j.biomaterials.2022.121491

Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus

Kamatani, Takashi; Hagizawa, Hiroki; Yarimitsu, Seido et al.

Biomaterials, 2022, 284, 121491

Number of Access:989（2025-07-24 02:34 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93297

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Title	Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus
Creator	CreatorName Kamatani, Takashi
	CreatorName Hagizawa, Hiroki
	NRID 1000090723205 1000090723205 CreatorName Yarimitsu, Seido
	CreatorName Morioka, Miho
	CreatorName Koyamatsu, Saeko
	NRID 1000010373317 1000010373317 CreatorName Sugimoto, Michihiko
	CreatorName Kodama, Joe
	NRID 1000010433278 1000010433278 CreatorName Yamane, Junko
	NRID 1000010433278 1000010433278 CreatorName Ishiguro, Hiroyuki
	NRID 1000070822435 1000070822435 CreatorName Shichino, Shigeyuki
	NRID 1000040240915 1000040240915 CreatorName Abe, Kuniya
	NRID 1000060273512 1000060273512 CreatorName Fujibuchi, Wataru
	NRID 1000020199300 1000020199300 CreatorName Fujie, Hiromichi
	NRID 1000070623982 1000070623982 ORCID 0000-0003-4882-2997 0000-0003-4882-2997 researchmap permalink 911_0 911_0 Scopus Author ID 25824322100 25824322100 CreatorName Kaito, Takashi
	NRID 1000050303938 1000050303938 ORCID 0000-0002-0520-3654 0000-0002-0520-3654 researchmap permalink cart cart Scopus Author ID 7004069586 7004069586 CreatorName Tsumaki, Noriyuki
Subject	Cartilage
	Chondrocytes
	Induced pluripotent stem cells
	intervertebral disc
	Nucleus pulposus
	Regeneration
Description	Kamatani T., Hagizawa H., Yarimitsu S., et al. Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus. Biomaterials 284, 121491 (2022); https://doi.org/10.1016/j.biomaterials.2022.121491.
Abstract	The loss of nucleus pulposus (NP) precedes the intervertebral disk (IVD) degeneration that causes back pain. Here, we demonstrate that the implantation of human iPS cell-derived cartilaginous tissue (hiPS-Cart) restores this loss by replacing lost NP spatially and functionally. NP cells consist of notochordal NP cells and chondrocyte-like NP cells. Single cell RNA sequencing (scRNA-seq) analysis revealed that cells in hiPS-Cart corresponded to chondrocyte-like NP cells but not to notochordal NP cells. The implantation of hiPS-Cart into a nuclectomized space of IVD in nude rats prevented the degeneration of the IVD and preserved its mechanical properties. hiPS-Cart survived and occupied the nuclectomized space for at least six months after implantation, indicating spatial and functional replacement of lost NP by hiPS-Cart. Further scRNA-seq analysis revealed that hiPS-Cart cells changed their profile after implantation, differentiating into two lineages that are metabolically distinct from each other. However, post-implanted hiPS-Cart cells corresponded to chondrocyte-like NP cells only and did not develop into notochordal NP cells, suggesting that chondrocyte-like NP cells are nearly sufficient for NP function. The data collectively indicate that hiPS-Cart is a candidate implant for regenerating NP spatially and functionally and preventing IVD degeneration.
Publisher	Elsevier Ltd
Source Title	Biomaterials
Volume (Issue)	284
Page	121491
Date of Issued	2022-05-01
Language	English
Handle URL	https://hdl.handle.net/11094/93297
PISSN	01429612
eISSN	18785905
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.biomaterials.2022.121491
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 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	Biomaterials. 2022, 284, p. 121491
DC.title	Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus
DC.creator	Kamatani, Takashi
	Hagizawa, Hiroki
	Yarimitsu, Seido
	Morioka, Miho
	Koyamatsu, Saeko
	Sugimoto, Michihiko
	Kodama, Joe
	Yamane, Junko
	Ishiguro, Hiroyuki
	Shichino, Shigeyuki
	Abe, Kuniya
	Fujibuchi, Wataru
	Fujie, Hiromichi
	Kaito, Takashi
	Tsumaki, Noriyuki
DC.publisher	Elsevier Ltd
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2022-05-01
DC.identifier	https://doi.org/10.1016/j.biomaterials.2022.121491
DC.subject	Cartilage
	Chondrocytes
	Induced pluripotent stem cells
	intervertebral disc
	Nucleus pulposus
	Regeneration
DC.description	Kamatani T., Hagizawa H., Yarimitsu S., et al. Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus. Biomaterials 284, 121491 (2022); https://doi.org/10.1016/j.biomaterials.2022.121491.
DCTERMS.abstract	The loss of nucleus pulposus (NP) precedes the intervertebral disk (IVD) degeneration that causes back pain. Here, we demonstrate that the implantation of human iPS cell-derived cartilaginous tissue (hiPS-Cart) restores this loss by replacing lost NP spatially and functionally. NP cells consist of notochordal NP cells and chondrocyte-like NP cells. Single cell RNA sequencing (scRNA-seq) analysis revealed that cells in hiPS-Cart corresponded to chondrocyte-like NP cells but not to notochordal NP cells. The implantation of hiPS-Cart into a nuclectomized space of IVD in nude rats prevented the degeneration of the IVD and preserved its mechanical properties. hiPS-Cart survived and occupied the nuclectomized space for at least six months after implantation, indicating spatial and functional replacement of lost NP by hiPS-Cart. Further scRNA-seq analysis revealed that hiPS-Cart cells changed their profile after implantation, differentiating into two lineages that are metabolically distinct from each other. However, post-implanted hiPS-Cart cells corresponded to chondrocyte-like NP cells only and did not develop into notochordal NP cells, suggesting that chondrocyte-like NP cells are nearly sufficient for NP function. The data collectively indicate that hiPS-Cart is a candidate implant for regenerating NP spatially and functionally and preventing IVD degeneration.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93297
citation_title	Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus
citation_author	Kamatani, Takashi
	Hagizawa, Hiroki
	Yarimitsu, Seido
	Morioka, Miho
	Koyamatsu, Saeko
	Sugimoto, Michihiko
	Kodama, Joe
	Yamane, Junko
	Ishiguro, Hiroyuki
	Shichino, Shigeyuki
	Abe, Kuniya
	Fujibuchi, Wataru
	Fujie, Hiromichi
	Kaito, Takashi
	Tsumaki, Noriyuki
citation_publisher	Elsevier Ltd
citation_language	English
citation_date	2022-05-01
citation_journal_title	Biomaterials
citation_volume	284
citation_firstpage	121491
citation_doi	https://doi.org/10.1016/j.biomaterials.2022.121491
citation_public_url	https://hdl.handle.net/11094/93297

Human iPS cell-derived cartilaginous tissue spatially and functionally replaces nucleus pulposus

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