Laboratory for Organ Regeneration | RIKEN BDR

Laboratory for Organ Regeneration

Team Leader

Takashi TsujiPh.D.

Photo of principal investigator

  • Location:Kobe / Developmental Biology Buildings
  • E-mail:takashi.tsuji[at]riken.jpPlease replace [at] with @.
  • Lab Website

Research and development of bioengineered organs and their clinical applications

Research Summary

Organogenesis begins with the formation of patterned developmental fields during early embryogenesis, which provide environments appropriate for the induction of specific organs. Most organs emerge from primordia induced by interactions between epithelial and mesenchymal tissue and, following organ-specific morphological changes, develop into functional structures.
Our group is working to gain a more complete understanding of the roles of epithelial-mesenchymal interactions in organ induction, development, and morphogenesis. Using technologies developed in our group for the three-dimensional (3D) control of epithelial stem cells and mesenchymal stem cells, we have generated regenerative primordia for teeth, hair follicles and endocrine tissue, such as salivary glands, and shown that these functionally integrate with surrounding tissue following transplantation into adult mice. By recapitulating organogenetic fields as seen in the early embryo to steer the self-organized formation of 3D tissue-like structures from pluripotent stem cells, such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), we seek both to elucidate the mechanisms by which such fields induce organogenesis and to develop new technologies for use in regenerative medicine. Building on these fundamental studies, we are now working to develop technologies for uses in therapeutic organ regeneration such as next-generation tooth regeneration implants and hair follicle regeneration for alopecia.

Mouse iPS cell-derived hair

Bioengineered hair follicle

Bioengineered tooth

Research Theme

  • Development of organ regeneration technology by applying organ development patterns
  • Development of hair follicle organ regenerative therapy
  • Development of the next-generation of Bio-hybrid implant for tooth regeneration
  • Research and Development of the next-generation 3D-integumentary organ system in vitro
  • Analysis of mechanisms underlying organogenesis using four-dimensional cell tracking system
  • Development of three-dimensional organ cultivation system in vitro

Main Publications List

  • Ishikawa J, Takeo M, Iwadate A, et al.
    Mechanical homeostasis of liver sinusoid is involved in the initiation and termination of liver regeneration.
    Communications Biology 4. 409 (2021) doi: 10.1038/s42003-021-01936-2
  • Takeo M, Asakawa K, Toyoshima K, et al.
    Expansion and characterization of epithelial stem cells with potential for cyclical hair regeneration.
    Scientific Reports (2021) doi: 10.1038/s41598-020-80624-3
  • Kimura S, Tsuchiya A, Ogawa M, et al.
    Tissue-scale tensional homeostasis in skin regulates structure and physiological function.
    Communications Biology 3. 637 (2020) doi: 10.1038/s42003-020-01365-7
  • Tanaka J, Ogawa M, Hojo H, et al.
    Generation of orthotopically functional salivary gland from embryonic stem cells.
    Nature Communications 9. 4216 (2018) doi: 10.1038/s41467-018-06469-7
  • Bin BH, Bhin J, Takaishi M, et al.
    Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10-p63 axis in epithelial homeostasis.
    Proceedings of the National Academy of Sciences of the United States of America 114(46). 12243–12248 (2017) doi : 10.1073/pnas.1710726114
  • Takagi R, Ishimaru J, Sugawara A, et al.
    Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model.
    Science Advances 2(4). e1500887 (2016) doi:10.1126/sciadv.1500887
  • Ozone C, Suga H, Eiraku M, et al.
    Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells.
    Nature Communications 7. 10351 (2016) doi:10.1038/ncomms10351
  • Ogawa M, Oshima M, Imamura A, et al.
    Functional salivary gland regeneration by transplantation of a bioengineered organ germ.
    Nature Communications 4. 2498 (2013) doi:10.1038/ncomms3498
  • Toyoshima KE, Asakawa K, Ishibashi N, et al.
    Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches.
    Nature Communications 3. 784 (2012) doi:10.1038/ncomms1784
  • Ikeda E, Morita R, Nakao K, et al.
    Fully functional bioengineered tooth replacement as an organ replacement therapy.
    Proceedings of the National Academy of Sciences of the United States of America 106. 13475–13480 (2009) doi: 10.1073/pnas.0902944106