Efficient cartilage generation from human progenitors by recapitulating transient vascularization

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659785
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Plastic surgery
• Research Institution: Yokohama City University
• Principal Investigator: TAKEBE Takanori 横浜市立大学, 医学部, 准教授 (20612625)
• Co-Investigator(Kenkyū-buntansha): TANIGUCHI Hideki 横浜市立大学, 医学研究科, 教授 (70292555) ; KOBAYASHI Shinji 横浜市立大学, 医学研究科, 客員准教授 (90464536)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 移植・再生医療 / 再生医学

Research Abstract

Here, we report that avascular elastic cartilage could be efficiently regenerated from in vitro grown mesenchymal condensation by recapitulating early chondrogenesis. Combined with an intravital imaging approach, we identified the presence of endothelial cells inside the mesenchymal condensation prior to cartilage maturation. Strikingly, recreating endothelial interaction in culture enabled the recently identified adult progenitors to generate a mesenchymal condensation in vitro in a self-driven manner without any support of exogenous factors nor scaffolds. These in vitro grown 3-D condensed progenitors much efficiently reconstructed three-dimensional elastic cartilage upon transplantation compared with conventional methods. Thus, the transplantation of condensed progenitors with endothelial cells represents a promising new approach towards realizing regenerative medicine as well as studying the mechanism of vascular regression.

Research Products

• [Journal Article] Reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage (2014)
  • Author(s): Mitsuru Mizuno, Shinji Kobayashi, Takanori Takebe, Hiroomi Kan, Yuichiro Yabuki, Takahisa Matsuzaki, Hiroshi Y. Yoshikawa, Seiichiro Nakabayashi, Lee JeongIk, Jiro Maegawa, Hideki Taniguchi
  • Journal Title: Stem Cells Volume: 32(3) Pages: 816-821
  • DOI: 10.1002/stem.1529
  • Peer Reviewed
• [Journal Article] Generation of a vascularized and functional human liver from an iPSC-derived organ bud transplant (2014)
  • Author(s): Takanori Takebe, Ran-Ran Zhang, Hiroyuki Koike, Masaki Kimura, Emi Yoshizawa, Masahiro Enomura, Keisuke Sekine, Hideki Taniguchi
  • Journal Title: Nature Protocols Volume: 9(2) Pages: 396-409
  • DOI: 10.1038/nprot.2014.020
  • Peer Reviewed
• [Journal Article] Vascularized and functional human liver from an iPSC-derived organ bud transplant (2013)
  • Author(s): Takanori Takebe, Keisuke Sekine, Masahiro Enomura, Hiroyuki Koike, Ran-Ran Zhang, Yasuharu Ueno, Yun-Wen Zheng, Naoto Koike, Shinsuke Aoyama, Yasuhisa Adachi, Hideki Taniguch
  • Journal Title: Nature Volume: 499 Pages: 481-484
  • DOI: 10.1038/nature12271
  • Peer Reviewed
• [Presentation] 臓器原基創出法を活用した多細胞系からなる複雑な立体組織の人為的構成 (2014)
  • Author(s): 武部貴則、吉川洋史、谷口英樹
  • Organizer: 第13回日本再生医療学会
  • Place of Presentation: 国立京都国際会館(京都府)シンポジウム
  • Year and Date: 20140304-06
  • Invited
• [Presentation] Phenotypic comparison of canine articular and auricular derived chondrocytes for cartilage reconstruction (2013)
  • Author(s): Mizuno M, Takebe T, Kobayashi S, Lee S, Jo YH, Lee JI, Taniguchi H
  • Organizer: The 13th Congress of the Asian Society of Transplantation
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20130902-06
• [Presentation] Transient vascularization directs intrinsic cartilage formation from human progenitors (2013)
  • Author(s): Takebe T, Kobayashi S, Mizuno M, Suzuki H, Chang Yu-Min, Yoshizawa E, Maegawa J, Taniguchi H
  • Organizer: International Society for Stem Cell Research 11^<th> annual meeting
  • Place of Presentation: Boston, USA(Poster)
  • Year and Date: 20130612-15
• [Presentation] ヒト耳介由来軟骨前駆細胞を用いた弾性軟骨再構築法の開発 (2013)
  • Author(s): 武部貴則、小林眞司、谷口英樹
  • Organizer: 第12回日本再生医療学会シンポジウム「組織幹細胞の最前線」
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 20130321-23
• [Presentation] Reconstitution of Articular(joint) cartilage defects by auricle(ear) derived stem/ progenitor cells (2012)
  • Author(s): Mizuno M, Kobayashi S, Takebe T, Suzuki H, Murata S, Yabuki Y, Hirotomi K, Yasumura K, Maegawa J, Taniguchi H
  • Organizer: International Society for Stem Cell Research 10^<th> annual meeting
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 20120613-16
• [Presentation] ヒト耳介軟骨膜由来幹/前駆細胞を用いた弾性軟骨再構築法の開発 (2012)
  • Author(s): 武部貴則、小林眞司、矢吹雄一郎、鈴木啓、水野満、安村和正、広富浩一、鄭允文、前川二郎、谷口英樹
  • Organizer: 第11回日本再生医療学会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 20120612-14
• [Remarks]
  • URL: http://www-user.yokohama-cu.ac.jp/~saisei/
• [Patent(Industrial Property Rights)] 軟骨細胞の調製方法 (2014)
  • Inventor(s): 武部貴則(50%),谷口英樹(35%),小林眞司(15%)
  • Industrial Property Rights Holder: 武部貴則(50%),谷口英樹(35%),小林眞司(15%)
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT/JP2014/57673
  • Acquisition Date: 2014-03-20
  • Overseas
• [Patent(Industrial Property Rights)] 生物学的組織に血管系を付与する方法 (2013)
  • Inventor(s): 武部貴則, 谷口英樹, 高橋禎暢
  • Industrial Property Rights Holder: 武部貴則, 谷口英樹, 高橋禎暢
  • Industrial Property Rights Type: 特願
  • Industrial Property Number: 2013-153056
  • Filing Date: 2013-07-23