Development of chondrocyte differentiation method from human iPS cells

• Project/Area Number: 26293330
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: SAITO Taku 東京大学, 医学部附属病院, 講師 (30456107)
• Co-Investigator(Kenkyū-buntansha): 門野 夕峰 東京大学, 医学部附属病院, 准教授 (70401065) ; 矢野 文子 東京大学, 医学部附属病院, 助教 (80529040)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000); Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 整形外科学 / 変形性関節症 / 再生医療学 / 軟骨再生 / 再生医学 / iPS細胞 / 軟骨細胞 / 再生医療

Outline of Final Research Achievements

iPS cell is attractive cell source for regenerative medicine. The present study has established a novel chondrocyte induction protocol from human iPS cells by only two chemical compounds within one week. We did not find any undifferentiated cells after one week culture by the protocol, indicating the markedly high efficiency. When we implanted the differentiated cells into mouse knee joints, hyaline cartilage formation was observed.

Research Products

• [Journal Article] Different Regulation of Limb Development by p63 Transcript Variants. (2017)
  • Author(s): Kawata M, Taniguchi Y, Mori D, Yano F, Ohba S, Chung UI, Shimogori T, Mills AA, Tanaka S, Saito T
  • Journal Title: PLOS ONE Volume: 12
  • DOI: 10.1371/journal.pone.0174122
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Targeting gene expression to specific cells of kidney tubules in vivo, using adenoviral promoter fragments (2017)
  • Author(s): Sumiyo Watanabe , Toru Ogasawara, Yoshifuru Tamura, Taku Saito, Toshiyuki Ikeda, Nobuchika Suzuki, Tatsuo Shimosawa, Shigeru Shibata, Ung-il Chung, Masaomi Nangaku, Shunya Uchida
  • Journal Title: PLOS One Volume: 12 Pages: 1-14
  • DOI: 10.1371/journal.pone.0168638
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regulation of Chondrocyte Survival in Mouse Articular Cartilage by p63 (2017)
  • Author(s): Taniguchi Y, Kawata M, Chang SH, Mori D, Okada K, Kobayashi H, Sugita S, Hosaka Y, Inui H, Taketomi S, Yano F, Ikeda T, Akiyama H, Mills AA, Chung UI, Tanaka S, Kawaguchi H, and Saito T*
  • Journal Title: Arthritis & Rheumatology Volume: 69 Pages: 598-609
  • DOI: 10.1002/art.39976
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes (2016)
  • Author(s): Kobayashi H, Chang S, Mori D, Itoh S, Hirata M, Hosaka Y, Taniguchi Y, Okada K, Mori Y, Yano F, Chung U, Akiyama H, Kawaguchi H, Tanaka S, Saito T.
  • Journal Title: Nat Commun. Volume: 7 Pages: 13336-13336
  • DOI: 10.1038/ncomms13336
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. (2016)
  • Author(s): H. Aini, K. Itaka, A. Fujisawa, H. Uchida, S. Uchida, S. Fukushima, K. Kataoka, T. Saito, U. -I. Chung, S. Ohba
  • Journal Title: Sci. Rep. Volume: 6 Pages: 18743-18743
  • DOI: 10.1038/srep18743
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Comparison of mouse and human ankles and establishment of mouse ankle osteoarthritis models by surgically-induced instability. (2016)
  • Author(s): Chang SH, Yasui T, Taketomi S, Matsumoto T, Kim-Kaneyama JR, Omiya T, Hosaka Y, Inui H, Omata Y, Yamagami R, Mori D, Yano F, Chung U, Tanaka S, Saito T.
  • Journal Title: Osteoarthritis Cartilage. Volume: 24 Pages: 688-697
  • DOI: 10.1016/j.joca.2015.11.008
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] <b>Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem </b><b>cells </b> (2015)
  • Author(s): Saito T, Yano F, Mori D, Kawata M, Hoshi K, Takato T, Masaki H, Otsu M, Eto K, Nakauchi H, Chung UI, Tanaka S
  • Journal Title: Biomed. Res. Volume: 36 Issue: 3 Pages: 179-186
  • DOI: 10.2220/biomedres.36.179
  • NAID: 130005083858
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transcription factor Hes1 modulates osteoarthritis development in cooperation with calcium/calmodulin-dependent protein kinase 2 (2015)
  • Author(s): Sugita S, Taketomi S, Saito T, et al.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 112 Pages: 3080-3085
  • DOI: 10.1073/pnas.1419699112
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice. (2015)
  • Author(s): Tokuyama N, Hirose J, Omata Y, Yasui T, Izawa N, Matsumoto T, Masuda H, Ohmiya T,Yasuda H, Saito T, Kadono Y, Tanaka S
  • Journal Title: Bone Reports. Volume: 2 Pages: 1-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] <b>Regulation of mouse chondrocyte differentiation by CCAAT/enhancer-binding pr</b><b>oteins </b> (2015)
  • Author(s): Okuma T, Hirata M, Yano F, Mori D, Kawaguchi H, Chung UI, Tanaka S, Saito T
  • Journal Title: Biomed. Res. Volume: 36 Issue: 1 Pages: 21-29
  • DOI: 10.2220/biomedres.36.21
  • NAID: 130004903876
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genomewide Comprehensive Analysis Reveals Critical Cooperation Between Smad and c-Fos in RANKL-Induced Osteoclastogenesis. (2015)
  • Author(s): Omata Y, Yasui T, Hirose J, Izawa N, Imai Y, Matsumoto T, Masuda H, Tokuyama N, Nakamura S, Tsutsumi S, Yasuda H, Okamoto K, Takayanagi H, Hikita A, Imamura T, Matsuo K, Saito T, Kadono Y, Aburatani H, Tanaka S
  • Journal Title: Journal of Bone and Mineral Research Volume: 30 Pages: 869-77
  • DOI: 10.1002/jbmr.2418
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of SCAN Domain Zinc-Finger Gene ZNF449 as a Novel Factor of Chondrogenesis (2014)
  • Author(s): Okada K, Saito T, et al.
  • Journal Title: PLoS One Volume: 9
  • DOI: 10.1371/journal.pone.0115169
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SOX10 Transactivates S100B to Suppress Schwann Cell Proliferation and to Promote Myelination. (2014)
  • Author(s): Fujiwara S, Hoshikawa S, Ueno T, Hirata M, Saito T, Ikeda T, Kawaguchi H, Nakamura K, Tanaka S, Ogata T
  • Journal Title: PLoS One Volume: 9
  • DOI: 10.1371/journal.pone.0115400
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Determination of differential gene expression profiles in superficial and deeper zones of mature rat articular cartilage using RNA sequencing of laser microdissected tissue specimens. (2014)
  • Author(s): Mori Y, Chung UI, Tanaka S, Saito T
  • Journal Title: Biomed Res Volume: 35 Pages: 263-70
  • NAID: 130004678582
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] S100A1 and S100B are dispensable for endochondral ossification during skeletal development (2014)
  • Author(s): Mori Y, Mori D, Chung UI, Tanaka S, Heierhorst J, Buchou T, Baudier J, Kawaguchi H, Saito T
  • Journal Title: Biomed Res Volume: 35 Pages: 243-50
  • NAID: 130004678580
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Disease-modifying effects of TD-198946 on progressed osteoarthritis in a mouse model (2014)
  • Author(s): Yano F, Saito T, et al.
  • Journal Title: Ann Rheum Dis Volume: 73 Pages: 2062-2064
  • DOI: 10.1136/annrheumdis-2014-205672
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Stepwise Differentiation of Pluripotent Stem Cells into Osteoblasts Using Four Small Molecules under Serum-free and Feeder-free Conditions (2014)
  • Author(s): Kanke K, Masaki H, Saito T, Komiyama Y, Hojo H, Nakauchi H, Lichtler AC, Takato T, Chung UI, Ohba S
  • Journal Title: Stem Cell Reports Volume: 6 Pages: 751-60
  • DOI: 10.1016/j.stemcr.2014.04.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of fibroblast growth factor-18 as a molecule to protect adult articular cartilage by gene expression profiling (2014)
  • Author(s): Mori Y, Saito T, Chang SH, Kobayashi H, Ladel CH, Guehring H, Chung UI, Kawaguchi H.
  • Journal Title: J Biol Chem. Volume: 289 Pages: 10192-200
  • DOI: 10.1074/jbc.m113.524090
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] NF-kB/TNF-a positive feedback loop with active proteasome machinery supports myeloid leukemia initiating cell capacity. (2014)
  • Author(s): Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y, Kurokawa M.
  • Journal Title: Journal of Clinical Investigation Volume: 124 Pages: 528-42
  • DOI: 10.1172/jci68101
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 過剰な力学的ストレス負荷による関節軟骨変性の分子メカニズム (2016)
  • Author(s): 齋藤琢
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-12-02
  • Invited
• [Presentation] 変性性関節症の制御メカニズム (2016)
  • Author(s): 齋藤琢
  • Organizer: Orthopedic Research Club
  • Place of Presentation: 木更津
  • Year and Date: 2016-11-19
  • Invited
• [Presentation] 過剰な力学的ストレスによる関節軟骨異化のメカニズム (2016)
  • Author(s): 齋藤琢
  • Organizer: 第10回骨軟骨フロンティア
  • Place of Presentation: 東京
  • Year and Date: 2016-11-05
  • Invited
• [Presentation] Regulation of Articular Cartilage Homeostasis and Osteoarthritis Development by the NF-kappaB signaling. (2016)
  • Author(s): Taku Saito
  • Organizer: 2016 Cold Spring Harbor Asia Conference on Bone & Cartilage
  • Place of Presentation: Suzhou, China
  • Year and Date: 2016-10-26
  • Int'l Joint Research / Invited
• [Presentation] Notch・Hes1による軟骨細胞の制御機構 (2016)
  • Author(s): 齋藤琢
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2016-10-13
  • Invited
• [Presentation] 過剰な力学的ストレスによる関節軟骨異化のメカニズム (2016)
  • Author(s): 齋藤琢
  • Organizer: 第34回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-07-21
  • Invited
• [Presentation] Perspective of disease-modifying osteoarthritis drugs (2016)
  • Author(s): Taku Saito
  • Organizer: 第3回アジア太平洋骨代謝学会議
  • Place of Presentation: 大阪
  • Year and Date: 2016-07-20
  • Int'l Joint Research / Invited
• [Presentation] Establishment of Surgical Destabilization Model of Mouse Ankle Osteoarthritis (2015)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Annual meeting of the Orthopaedic Research Society.
  • Place of Presentation: Las vegas, USA
  • Year and Date: 2015-03-28 – 2015-03-31
• [Presentation] 軟骨内骨化研究から生まれる実用的研究 (2014)
  • Author(s): 齋藤琢
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-10
  • Invited
• [Presentation] 変形性関節症への応用を目指した軟骨再生研究 (2014)
  • Author(s): 齋藤琢
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-09
  • Invited
• [Presentation] HIF-1α IS ESSENTIAL FOR ARTICULAR CARTILAGE HOMEOSTASIS THROUGH INDUCTION OF ANABOLIC FACTORS AND SUPPRESSION OF CATABOLIC FACTORS. (2014)
  • Author(s): Okada K, Saito T, et al.
  • Organizer: Annual meeting of the American Society for bone and mineral research.
  • Place of Presentation: Houston USA
  • Year and Date: 2014-09-16
• [Presentation] Identification of Grem1 as a catabolic factor induced by mechanical stress loading in articular chondrocyte. (2014)
  • Author(s): Chang SH, Saito T, et al.
  • Organizer: Annual meeting of the American Society for bone and mineral research.
  • Place of Presentation: Houston USA
  • Year and Date: 2014-09-15
• [Presentation] Expression and function of CCAAT/enhancer-binding protein family in chondrocytes. (2014)
  • Author(s): Okuma T, Saito T, et al.
  • Organizer: Annual meeting of the American Society for bone and mineral research.
  • Place of Presentation: Houston USA
  • Year and Date: 2014-09-12
• [Presentation] 変形性関節症の制御メカニズムの解明 (2014)
  • Author(s): 齋藤琢
  • Organizer: 第32回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-07-25
  • Invited
• [Presentation] Research on pathophysiology and therapeutic target of osteoarthritis. (2014)
  • Author(s): Taku Saito
  • Organizer: 16th Asia Pacific League of Associations for Rheumatology Congress (APLAR)
  • Place of Presentation: Cebu City, Philippines
  • Year and Date: 2014-04-04
  • Invited
• [Remarks] 東京大学医学部整形外科
  • URL: http://www.u-tokyo-ortho.jp/
• [Patent(Industrial Property Rights)] 軟骨細胞の製造方法 (2016)
  • Inventor(s): 齋藤琢、ほか
  • Industrial Property Rights Holder: 齋藤琢、ほか
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2016-163872
  • Filing Date: 2016-08-24