Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

Abe, Kengo; Yamashita, Akihiro; Morioka, Miho; Horike, Nanao; Takei, Yoshiaki; Koyamatsu, Saeko; Okita, Keisuke; Matsuda, Shuichi; Tsumaki, Noriyuki

doi:https://doi.org/10.1038/s41467-023-36408-0

Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

Abe, Kengo; Yamashita, Akihiro; Morioka, Miho et al.

Nature Communications, 2023, 14(1), 804

Number of Access:653（2025-09-01 13:10 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93295

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Title	Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect
Creator	NRID 1000010983546 1000010983546 CreatorName Abe, Kengo
	NRID 1000000636855 1000000636855 researchmap permalink Aki_yama26 Aki_yama26 Scopus Author ID 56404044900 56404044900 CreatorName Yamashita, Akihiro
	CreatorName Morioka, Miho
	NRID 1000030589221 1000030589221 researchmap permalink banana banana CreatorName Horike, Nanao
	CreatorName Takei, Yoshiaki
	researchmap permalink saeko0803 saeko0803 CreatorName Koyamatsu, Saeko
	NRID 1000090512434 1000090512434 CreatorName Okita, Keisuke
	NRID 1000040294938 1000040294938 CreatorName Matsuda, Shuichi
	NRID 1000050303938 1000050303938 ORCID 0000-0002-0520-3654 0000-0002-0520-3654 researchmap permalink cart cart Scopus Author ID 7004069586 7004069586 CreatorName Tsumaki, Noriyuki
Description	Abe K., Yamashita A., Morioka M., et al. Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect. Nature Communications 14, 804 (2023); https://doi.org/10.1038/s41467-023-36408-0.
Abstract	Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as are remodeled as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage; however further assessment of functional recovery long term after load bearing injuries is required.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	14(1)
Page	804
Date of Issued	2023-02-20
Language	English
Handle URL	https://hdl.handle.net/11094/93295
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-023-36408-0
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	Nature Communications. 2023, 14(1), p. 804
DC.title	Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect
DC.creator	Abe, Kengo
	Yamashita, Akihiro
	Morioka, Miho
	Horike, Nanao
	Takei, Yoshiaki
	Koyamatsu, Saeko
	Okita, Keisuke
	Matsuda, Shuichi
	Tsumaki, Noriyuki
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2023-02-20
DC.identifier	https://doi.org/10.1038/s41467-023-36408-0
DC.description	Abe K., Yamashita A., Morioka M., et al. Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect. Nature Communications 14, 804 (2023); https://doi.org/10.1038/s41467-023-36408-0.
DCTERMS.abstract	Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as are remodeled as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage; however further assessment of functional recovery long term after load bearing injuries is required.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93295
citation_title	Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect
citation_author	Abe, Kengo
	Yamashita, Akihiro
	Morioka, Miho
	Horike, Nanao
	Takei, Yoshiaki
	Koyamatsu, Saeko
	Okita, Keisuke
	Matsuda, Shuichi
	Tsumaki, Noriyuki
citation_publisher	Nature Research
citation_language	English
citation_date	2023-02-20
citation_journal_title	Nature Communications
citation_volume	14
citation_issue	1
citation_firstpage	804
citation_doi	https://doi.org/10.1038/s41467-023-36408-0
citation_public_url	https://hdl.handle.net/11094/93295

Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect

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