Project Summary

We have been developing new methods to induce epithelial tissue from the skin ulcer surface de novo (#1, 2) and skin appendages such as hair follicles and sebaceous glands (#3), which are complex tissues composed of epithelial and mesenchymal cells, as a new treatment for intractable skin ulcers and ischemic limb necrosis, an urgent issue for plastic surgeons in Japan, with an aging population.

In this project, we are working to develop therapeutic intervention methods to obtain major complex complex tissue regeneration in vivo and in complex tissues, utilizing the development scheme we have been working on to date.

In the initial phase of the feasibility study, we aim to develop a method to regenerate lost limbs (limb regeneration) and other tissues and organs by gene transfer into the bodies of mammalian animals.

We will also develop methods to rejuvenate tissues related to the quality of life of the elderly, such as skin, muscles, and bones, through gene transfer of embryonizing factors that have been identified.

Epigenetic changes (#4) and single cell gene expression analysis (#5) are being used to develop limb regeneration methods for this research. We are also developing novel gene transfer methods for clinical application (#3) and DDS for bio-local approaches (#6, 7).

R&D　Team

Masakazu Kurita, The University of Tokyo (Program manager)

Hironori Hojo, The University of Tokyo

Keiichiro Suzuki, Osaka University

Gojiro Nakagami, The University of Tokyo

Takamasa Sakai, The University of Tokyo

References

1) Kurita et al. In vivo reprogramming of wound-resident cells generates skin epithelial tissue. Nature. 2018; 561: 243-247

2) Kurita et al. Development of de novo epithelialization method for treatment of cutaneous ulcers. Journal of Dermatological Science. 2019; 95: 8-12

3) Moriwaki et al. In vivo reprogramming of wound resident cells generates skin with hair. 2003 https://doi.org/10.1101/2023.03.05.531138

4) Hojo et al. Runx2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages. 2022;40(10):111315.

5) Tani et al. Stem cell-based modeling and single-cell multiomics reveal gene-regulatory mechanisms underlying human skeletal development. 2023 Mar 20;112276..  

6) Ishikawa et al. Molecular Weight-dependent Diffusion, Biodistribution, and Clearance Behavior of Tetra-armed Poly(ethylene glycol) Subcutaneously Injected into the Back of Mice ACS Macro Lett. 2023

7) Kato et al. In situ-formable, dynamic crosslinked poly(ethylene glycol) carrier for localized adeno-associated virus infection and reduced off-target effects. Commun Biol 6, 508 (2023). 

Associated movies (with English caption)