Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage

Takei, Yoshiaki; Morioka, Miho; Yamashita, Akihiro; Kobayashi, Tomohito; Shima, Nobuyuki; Tsumaki, Noriyuki

doi:https://doi.org/10.1038/s41598-020-69641-4

Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage

Takei, Yoshiaki; Morioka, Miho; Yamashita, Akihiro et al.

Scientific Reports, 2020, 10(1), 12794

Number of Access:474（2025-09-01 13:10 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93304

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Title	Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage
Creator	CreatorName Takei, Yoshiaki
	CreatorName Morioka, Miho
	NRID 1000000636855 1000000636855 researchmap permalink Aki_yama26 Aki_yama26 Scopus Author ID 56404044900 56404044900 CreatorName Yamashita, Akihiro
	CreatorName Kobayashi, Tomohito
	CreatorName Shima, Nobuyuki
	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	Takei Y., Morioka M., Yamashita A., et al. Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage. Scientific Reports 10, 12794 (2020); https://doi.org/10.1038/s41598-020-69641-4.
Abstract	Articular cartilage damage does not heal spontaneously and causes joint dysfunction. The implantation of induced pluripotent stem cell (iPSC)-derived cartilage (iPS-Cart) is one candidate treatment to regenerate the damaged cartilage. However, concerns of tumorigenicity are associated with iPS-Cart, because the iPSC reprogramming process and long culture time for cartilage induction could increase the chance of malignancy. We evaluated the tumorigenic risks of iPS-Cart using HeLa cells as the reference. Spike tests revealed that contamination with 100 HeLa cells in 150 mg of iPS-Cart accelerated the cell growth rate. On the other hand, 150 mg of iPS-Cart without HeLa cells reached growth arrest and senescence after culture, suggesting less than 100 tumorigenic cells, assuming they behave like HeLa cells, contaminated iPS-Cart. The implantation of 10,000 or fewer HeLa cells into joint surface defects in the knee joint of nude rat did not cause tumor formation. These in vitro and in vivo studies collectively suggest that the implantation of 15 g or less iPS-Cart in the knee joint does not risk tumor formation if assuming that the tumorigenic cells in iPS-Cart are equivalent to HeLa cells and that nude rat knee joints are comparable to human knee joints in terms of tumorigenicity. However, considering the limited immunodeficiency of nude rats, the clinical amount of iPS-Cart for implantation needs to be determined cautiously.
Publisher	Nature Research
Source Title	Scientific Reports
Volume (Issue)	10(1)
Page	12794
Date of Issued	2020-07-30
Language	English
Handle URL	https://hdl.handle.net/11094/93304
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41598-020-69641-4
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	Scientific Reports. 2020, 10(1), p. 12794
DC.title	Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage
DC.creator	Takei, Yoshiaki
	Morioka, Miho
	Yamashita, Akihiro
	Kobayashi, Tomohito
	Shima, Nobuyuki
	Tsumaki, Noriyuki
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2020-07-30
DC.identifier	https://doi.org/10.1038/s41598-020-69641-4
DC.description	Takei Y., Morioka M., Yamashita A., et al. Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage. Scientific Reports 10, 12794 (2020); https://doi.org/10.1038/s41598-020-69641-4.
DCTERMS.abstract	Articular cartilage damage does not heal spontaneously and causes joint dysfunction. The implantation of induced pluripotent stem cell (iPSC)-derived cartilage (iPS-Cart) is one candidate treatment to regenerate the damaged cartilage. However, concerns of tumorigenicity are associated with iPS-Cart, because the iPSC reprogramming process and long culture time for cartilage induction could increase the chance of malignancy. We evaluated the tumorigenic risks of iPS-Cart using HeLa cells as the reference. Spike tests revealed that contamination with 100 HeLa cells in 150 mg of iPS-Cart accelerated the cell growth rate. On the other hand, 150 mg of iPS-Cart without HeLa cells reached growth arrest and senescence after culture, suggesting less than 100 tumorigenic cells, assuming they behave like HeLa cells, contaminated iPS-Cart. The implantation of 10,000 or fewer HeLa cells into joint surface defects in the knee joint of nude rat did not cause tumor formation. These in vitro and in vivo studies collectively suggest that the implantation of 15 g or less iPS-Cart in the knee joint does not risk tumor formation if assuming that the tumorigenic cells in iPS-Cart are equivalent to HeLa cells and that nude rat knee joints are comparable to human knee joints in terms of tumorigenicity. However, considering the limited immunodeficiency of nude rats, the clinical amount of iPS-Cart for implantation needs to be determined cautiously.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93304
citation_title	Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage
citation_author	Takei, Yoshiaki
	Morioka, Miho
	Yamashita, Akihiro
	Kobayashi, Tomohito
	Shima, Nobuyuki
	Tsumaki, Noriyuki
citation_publisher	Nature Research
citation_language	English
citation_date	2020-07-30
citation_journal_title	Scientific Reports
citation_volume	10
citation_issue	1
citation_firstpage	12794
citation_doi	https://doi.org/10.1038/s41598-020-69641-4
citation_public_url	https://hdl.handle.net/11094/93304

Quality assessment tests for tumorigenicity of human iPS cell-derived cartilage

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