RIKEN Center for Biosystems Dynamics Research Laboratory for Organ Regeneration

Team Leader: Takashi Tsuji (Ph.D.)

Japanese Page

Research Summary

Organogenesis begins with the formation of patterned organ-forming fields during embryogenesis, which provide environments appropriate for the induction of specific organs. Most organs emerge from organ germs induced by interactions between organ-inductive epithelial and mesenchymal stem cells and, following organ-specific morphogenesis, develop into functional structures. Our group is studying on the roles of epithelial-mesenchymal interactions during organ induction, development, and morphogenesis. Using technologies developed in our group for the three-dimensional (3D) manipulation of organ-inductive epithelial 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. We also focus on the cellar and molecular mechanisms on organ specific 3D-morphogenesis by using 4D-cell dynamics imaging techniques. 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 for missing tooth and hair follicle regeneration for alopecia.

Main Research Fields

Biology

Related Research Fields

Complex Systems
Medicine, Dentistry & Pharmacy
Biomedical engineering/Biomaterial science and engineering

Keywords

Regenerative Therapy
Organ Regeneration
Stem Cell Biology
Development of Medical Devices
Healthcare

Selected Publications

1. Jun I, et al.:
"Mechanical homeostasis of liver sinusoid is involved in the initiation and termination of liver regeneration."
Common Biol. 4, 409 (2021)
2. Makoto T, et al.:
"Expansion and characterization of epithelial stem cells with potential for cyclical hair regeneration"
Sci Rep. 11(1):1173 (2021)
3. Shun K, et al.:
"Tissue-scale tensional homeostasis in skin regulates structure and physiological function."
Common Biol. 3, 637 (2020)
4. Takagi R, et al.:
"Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model."
Sci. Adv. 1;2(4):e1500887 (2016)
5. Ozone C, et al.:
"Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells."
Nat Commun 7.10351 (2016)
6. Ogawa M, et al.:
"Functional salivary gland regeneration by transplantation of a bioengineered organ germ."
Nat Commun 4.2498 (2013)
7. Hirayama M, et al.:
"Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ."
Nat Commun 4.2497 (2013)
8. Toyoshima K. E, et al.:
"Fully functional hair follicle regeneration through the rearrangement of stem cells and their niches."
Nat Commun 3.784 (2012)
9. Ikeda E, et al.:
"Fully functional bioengineered tooth replacement as an organ replacement therapy."
Proc Natl Acad Sci U S A 106.13475-80 (2009)
10. Nakao K, et al.:
"The development of a bioengineered organ germ method."
Nat Methods 4.227-30 (2007)