Global analysis of congenital bone and joint diseases using a chondrogenic differentiation system from iPS cells

• Project/Area Number: 24591507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: UMEDA KATSUTUSGU 京都大学, 医学(系)研究科(研究院), 助教 (80397538)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: iPS細胞 / 骨・関節疾患 / 軟骨分化 / 軟骨 / 先天異常

Outline of Final Research Achievements

We addressed whether the pathogenesis of CINCA syndrome, a congenital bone and joint disease characterized by epiphyseal overgrowth, could be recapitulated by using neural crest-derived chondroprogenitor differentiation from using patient-derived iPS cells. 3D chondrogenic assays showed mutant iPS cells produced significantly huge chondrogenous pellets than wild type iPS cells. Furthermore, in vivo chongrogenic assays by subcutaneous xenotranplation into immunodeficient mice showed that huge chondrogenenous tissues, consisting of immature chondroprogenitors, were obtained, which recapitulates the pathological condition of the syndrome.

Research Products

• [Journal Article] Enhanced chondrogenesis of induced pluripotent stem cells from patients with neonatal-onset multisystem inflammatory disease occurs via the caspase 1-independent cAMP/protein kinase A/CREB pathway (2015)
  • Author(s): Yokoyama, K. Ikeya, M. Umeda, K. Oda, H. Nodomi, S. Nasu, A. Matsumoto, Y. Izawa, K. Horigome, K. Kusaka, T. Tanaka, T. Saito, M. K. Yasumi, T. Nishikomori, R. Ohara, O. Nakayama, N. Nakahata, T. Heike, T. Toguchida, J.
  • Journal Title: Arthritis Rheumatol Volume: 67 Issue: 1 Pages: 302-314
  • DOI: 10.1002/art.38912
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Selective development of myogenic mesenchymal cells from human embryonic and induced pluripotent stem cells (2012)
  • Author(s): Awaya T., Kato T., Mizuno Y., Chang H., Niwa A., Umeda K., Nakahata T., Heike T.
  • Journal Title: PLoS ONE Volume: 7(12) Issue: 12 Pages: e51638-e51638
  • DOI: 10.1371/journal.pone.0051638
  • NAID: 120005122354
  • Peer Reviewed
• [Journal Article] Human chondrogenic paraxial mesoderm, directed specification and prospective isolation from pluripotent stem cells. (2012)
  • Author(s): Umeda K, Zhao J, Simmons P, Stanley E, Elefanty A, Nakayama N
  • Journal Title: Sci Rep Volume: 2 Issue: 1 Pages: 455-455
  • DOI: 10.1038/srep00455
  • Peer Reviewed
• [Presentation] ヒト多能性幹細胞を用いた神経堤由来軟骨前駆細胞の大量増幅システムの開発 (2013)
  • Author(s): 梅田雄嗣、納富誠司郎、平家俊男、中山直樹
  • Organizer: 日本再生医療学会
  • Place of Presentation: 横浜市
• [Presentation] ヒト多能性幹細胞を用いた神経堤由来軟骨前駆細胞の大量増幅システムの開発 (2013)
  • Author(s): 梅田雄嗣、納富誠司郎、平家俊男、中山直樹
  • Organizer: 日本小児科学会総会
  • Place of Presentation: 広島市