Disease modeling and drug screening of thanatophooric dysplasia using reprogramming technology

• Project/Area Number: 24890101
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: Kyoto University
• Principal Investigator: YAMASHITA Akihiro 京都大学, iPS細胞研究所, 研究員 (00636855)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: iPS細胞 / 疾患 / 骨軟骨分化

Research Abstract

Thanatophoric dysplasia (TD) is a severe skeletal disorder caused by gain-of-function mutations in the fibroblast growth factor receptor-3 (FGFR3) gene. Patients with TD show short limbs and a narrow rib cage caused by abnormal cartilage formation. There are needs for drugs, however the disease mechanism is still unclear.
Here, we have generated induced pluripotent stem cells (iPSCs) from fibroblasts obtained from TD-patients. Then, we will understand disease mechanism and screen candidate drugs.

Research Products

• [Journal Article] Cartilage tissue engineering identifies abnormal human induced pluripotent stem cells (2013)
  • Author(s): Yamashita A, Liu S, Woltjen K, Thomas B, Meng G, Hotta A, Takahashi K, Ellis J, Yamanaka S, Rancourt DE
  • Journal Title: Sci Rep Volume: 3 Issue: 1 Pages: 1978-1978
  • DOI: 10.1038/srep01978
  • Peer Reviewed
• [Journal Article] Embryonic stem cells incorporate into newly formed bone and do not form tumors in an immunocompetent mouse fracture model (2013)
  • Author(s): Taiani JT, Krawetz RJ, Yamashita A, Pauchard Y, Buie HR, Ponjevic D, Boyd SK, Rancourt DE, Matyas JR
  • Journal Title: Cell Transplant Volume: 22(8) Issue: 8 Pages: 1453-62
  • DOI: 10.3727/096368912x658755
  • Peer Reviewed
• [Journal Article] Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors (2013)
  • Author(s): Outani H, Okada M, Yamashita A, Nakagawa K, Yoshikawa H, Tsumaki N.
  • Journal Title: PLoS One Volume: 8 Issue: 10 Pages: e77365-e77365
  • DOI: 10.1371/journal.pone.0077365
  • NAID: 120005333915
  • Peer Reviewed
• [Journal Article] iPS細胞由来軟骨細胞を用いた再生治療開発 (2013)
  • Author(s): 山下晃弘、妻木範行
  • Journal Title: Phama Medica Volume: 31巻4号(招待論文) Pages: 29-32
• [Journal Article] iPS細胞を使うー軟骨の研究へ (2013)
  • Author(s): 妻木範行、岡田稔、山下晃弘
  • Journal Title: 整形外科 Volume: 64巻10号(招待論文) Pages: 1106-1109
• [Journal Article] iPS細胞由来軟骨細胞を用いた再生治療開発 (2013)
  • Author(s): 山下晃弘, 妻木範行
  • Journal Title: Pharma Medica Volume: 31(4) Pages: 29-32
  • Peer Reviewed
• [Journal Article] Embryonic Stem Cells Incorporate into Newly Formed Bone and do not Form Tumors in an Immunocompetent Mouse Fracture Model. (2013)
  • Author(s): Taiani JT
  • Journal Title: Cell Transplant. Volume: in press
  • Peer Reviewed
• [Journal Article] iPS細胞由来軟骨細胞を用いた再生治療開発 (2013)
  • Author(s): 山下晃弘
  • Journal Title: Pharma Medica Volume: in press
• [Journal Article] Derivation of iPSCs in stirred suspension bioreactors (2012)
  • Author(s): Shafa M, Day B, Yamashita A, Meng G, Liu S, Krawetz R, Rancourt DE
  • Journal Title: Nat Methods Volume: 9(5) Issue: 5 Pages: 465-6
  • DOI: 10.1038/nmeth.1973
  • Peer Reviewed
• [Journal Article] Expansion and long term maintenance of induced pluripotent stem cells in stirred suspension bioreactors (2012)
  • Author(s): Shafa M, Sjonnesen K, Yamashita A, Liu S, Michalak M, Kallos MS, Rancourt DE
  • Journal Title: J of Tissue. Eng. Regen. Med Volume: 6(6) Issue: 6 Pages: 462-72
  • DOI: 10.1002/term.450
  • Peer Reviewed
• [Presentation] Derivation of transplantable cartilage from human induced pluripotent stem cells (2014)
  • Author(s): Yamashita A, Morioka M, Yahara Y, Okada M, Tsumaki N
  • Place of Presentation: Paris, France
• [Presentation] Abnormal chondrogenic differentiation of induced pluripotent stem cells established from patients with a severe skeletal disease, thanatophoric dysplasia (2014)
  • Author(s): Yamashita A, Tsumaki N
  • Organizer: Takeda symposium
  • Place of Presentation: Osaka, Japan
• [Presentation] Abnormal chondrogenic differentiation of induced pluripotent stem cells established from patients with a severe skeletal disease, thanatophoric dysplasia (2014)
  • Author(s): Yamashita A, Tsumaki N
  • Organizer: Takeda symposium
  • Place of Presentation: Takeda symposium
• [Presentation] ヒトiPS細胞から軟骨細胞への分化におけるGDF5の効果 (2013)
  • Author(s): 山下晃弘,妻木範行
  • Organizer: BMP研究会
  • Place of Presentation: 浜松
  • Year and Date: 2013-07-05
• [Presentation] Abnormal chondrogenic differentiation of induced pluripotent stem cells with a severe skeletal disease, thanatophoric dysplasia (2013)
  • Author(s): Yamashita A, Tsumaki N
  • Organizer: CiRA International Symposium 2013 Raising the Next Generation of Stem Cell Research
  • Place of Presentation: Kyoto, Japan
• [Presentation] ヒトiPS細胞から軟骨細胞への分化誘導 (2013)
  • Author(s): 山下晃弘,妻木範行
  • Organizer: ORC研究会
  • Place of Presentation: かずさ
• [Presentation] ヒトiPS細胞を用いた致死性骨異形成症の病態解明 (2013)
  • Author(s): 山下晃弘,妻木範行
  • Organizer: 日本炎症・再生学会
  • Place of Presentation: 京都(優秀演題賞受賞)
• [Presentation] ヒトiPS細胞を用いた致死性骨異形成症の病態解明 (2013)
  • Author(s): 山下晃弘, 妻木範行
  • Organizer: 日本炎症・再生学会
  • Place of Presentation: 京都
• [Presentation] ヒトiPS細胞から軟骨細胞への分化誘導 (2013)
  • Author(s): 山下晃弘, 妻木範行
  • Organizer: ORC研究会
  • Place of Presentation: 茨城
• [Presentation] Modeling and rescue of abnormal chondrogenic differentiation of induced pluripotent stem cells with a severe skeletal disease, thanatophoric dysplasia (2013)
  • Author(s): A Yamashita
  • Organizer: CiRA retreat 13
  • Place of Presentation: 滋賀
• [Presentation] The activation of c-MYC and LIN28B causes iPSC tumor formation during in vitro cartilage differentiation (2012)
  • Author(s): Yamashita A, Thomas B, Rancourt DE
  • Organizer: 10^<th> Annual Meeting of the International Society for Stem Cell Research
  • Place of Presentation: Yokohama, Japan
• [Presentation] ヒトiPS細胞から軟骨細胞への分化におけるGDF5の効果
  • Author(s): 山下晃弘, 妻木範行
  • Organizer: BMP研究会
  • Place of Presentation: 浜松