Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs

Stem Cell Reports
Akihiro YamashitaNoriyuki Tsumaki

Abstract

Defects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs). We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1), and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defe...Continue Reading

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Citations

Jan 27, 2016·Cellular and Molecular Life Sciences : CMLS·Heenam KwonKyriacos Athanasiou
Mar 25, 2016·Nature Communications·Yasuhito YaharaNoriyuki Tsumaki
May 9, 2015·Tissue Engineering. Part B, Reviews·Ryosuke SakataA Hari Reddi
Jul 7, 2016·Stem Cells International·Takanori Eguchi, Takuo Kuboki
Jul 28, 2016·Annals of the New York Academy of Sciences·Chathuraka T JayasuriyaQian Chen
Aug 5, 2016·Journal of Clinical Orthopaedics and Trauma·Yukihiko YasuiNorimasa Nakamura
Nov 1, 2016·Tissue Engineering. Part a·Takeshi KimuraNoriyuki Tsumaki
Feb 2, 2017·Cell Biology and Toxicology·Britta J H DriessenLucienne A Vonk
Feb 15, 2018·International Journal of Molecular Sciences·Ewelina StelcerWiktoria M Suchorska
Oct 27, 2017·Biotechnology Journal·Howard C TribeRahul S Tare
Jul 31, 2018·Journal of Tissue Engineering and Regenerative Medicine·Takumi TakahashiMasahiko Watanabe
Aug 22, 2018·Tissue Engineering. Part a·Xike ChenNoriyuki Tsumaki
Feb 16, 2019·Stem Cells Translational Medicine·Sergei A KuznetsovRaphael Gorodetsky
Jun 5, 2019·International Journal of Molecular Sciences·Michał Stefan LachWiktoria Maria Suchorska
Sep 5, 2019·International Journal of Molecular Sciences·Justyna BuchertWiltrud Richter
Jun 26, 2020·Development·Qin BianPatrick Cahan
Mar 4, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Jill M MiddendorfLawrence J Bonassar
Sep 17, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Kaoru AokiNaoto Saito
Apr 3, 2020·Nature·Mitsuhiro MatsudaCantas Alev
Jul 12, 2020·Journal of Tissue Engineering and Regenerative Medicine·Daichi TakizawaMasahiko Watanabe
Aug 1, 2020·Scientific Reports·Yoshiaki TakeiNoriyuki Tsumaki
May 17, 2018·Stem Cells International·Navneet Kumar DubeyWin-Ping Deng
Aug 2, 2017·The Journal of Clinical Investigation·Kyosuke HinoMakoto Ikeya
Jan 14, 2018·Journal of Experimental Orthopaedics·Kazunori ShimomuraNorimasa Nakamura
May 17, 2018·Stem Cells International·Yoojun NamJi Hyeon Ju
Jun 16, 2019·Cellular and Molecular Life Sciences : CMLS·Ryota Chijimatsu, Taku Saito
Mar 18, 2020·Scientific Reports·Rosie GriffithsSusan J Kimber

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Methods Mentioned

BETA
biopsies
fluorescence-activated cell sorting
FACS
PCR

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