3D human organ engineering for implantation and cell-based assay
—Optimization of 3D organization and mass transfer—

 
 

General goal and approaches of our lab

The general goal of our lab is the 3D organization of cultured organ/tissue-derived cells such as liver or pancreas cells in various scales for regenerative medicine and cell-based assay for drug or chemical screenings without having to resort to animal testing. In our body,
1) Cells are hierarchically organized at a very high cell density
2) The vascular system consistently supplies nutrients and removes waste/metabolites, thus attaining very high per-volume-based functionality.
However, full arrangement of such vascular systems in vitro is a challenging task to achieve due to the complexity of to simultaneously optimizing 3D high-density cellular organization and mass transfer between the cells and flow channels.

The most important step is to overcome the conflicting issues in various scales required by relevant applications. I believe academic knowledge of chemical engineering will give the basis for the optimization. For example, if we intend to organize large tissue equivalents for implantation therapy, the tissue should at least be arranged with a 3D branching/joining flow channel network as in vivo vasculature and the channels should be perfused with suitable culture medium containing oxygen carriers. Also, in order to make a small tissue for cell-based assays, we have to organize the cells to create an environment that the cells reorganize as their original tissues. At the same time, we need to pay special attention to mass transfers between the cells and the incubation medium, so that various kinetic parameters concerning metabolism are the same as those obtained in vivo. Chemical engineering undeniably gives a firm basis not only for analysis/description of these issues but also for further optimization and designing the suitable tissue-based devices/systems in various scales.

In order to realize cultured cell-based therapy or assays, we need to integrate knowledge and technologies from various disciplines in a well-balanced manner; that is, basic biology of growth, differentiation and maturation of human stem cells or organ progenitors, advanced engineering such as micropatterning, microfluidics, microfabrication or biomaterials, and medical or pharmaceutical knowledge about diseases and responses against therapy or administration of drugs. Due to the increasing complexity and versatility of current science and engineering, it is difficult to integrate the necessary technologies in one laboratory. We are therefore actively organizing and participating in collaborations with various research groups. To efficiently perform such objective-oriented integration, we use the objective-oriented frame of mind of chemical engineering. For example, we first set a final goal, then layout all the necessary knowledge and technologies with appropriate time points, and finally we implement the research and development along the roadmap. By doing this, the time for achieving the goal is minimized and even if some novel but unanticipated innovation emerges in related areas, we can judge the feasibility of relevant innovation. Even for regenerative medicine and development of cell-based assays, setting our basis on the chemical engineering discipline is important. Indeed, cell-culture related chemical engineering encompasses the basic biological findings and their applications via advanced engineering technologies.

Current scope of our lab

When engineers do research on human body systems, there are three typical approaches: from metabolism/biochemistry (the target is endoderm-derived organs), mechanics (mesoderm-derived organs) and informatics (ectoderm-derived organs). Because our main concerns are transport/metabolism-related aspect of the human body, our tentative targets are liver, pancreas or kidney for regenerative medicine and small intestine, lung, liver or kidney for cell-based assays. The typical research approach is as follows; first, design tissues in terms of cell-to-cell interaction and mass transfer according to the requirements of the relevant application, then culture stem/progenitor cells, and finally complete the devices/systems using advanced engineering technologies.

Message to future lab members

We welcome students or researches who have interest in 3D organ engineering. Since our lab participates in education and research at graduate levels (both master and doctoral courses), we seek motivated students not only from Tokyo University but also other universities all over the world. We also welcome postdoctoral researchers according to the financial situation. If you are interested in our lab, feel free to contact me (sakaiyasu[at]chemsys.t.u-tokyo.ac.jp) or Dr. Nishikawa (masaki[at]chemsys.t.u-tokyo.ac.jp), the research associate of our lab, and visit our lab. We can accept students from two departments in the Graduate School of Engineering; the Department of Chemical System Engineering and the Department of Bioengineering. Although there are no obvious differences in the thesis research, the curriculums are completely different, so please choose your department carefully.

Because we focus on the best integration of knowledge and technologies toward the final goal, I ask lab members to adopt an objective-oriented way of thinking and to constantly acquire knowledge about biosystems. Once you adopt such an attitude, you do not have to be afraid even if you happen to hold a completely different position in the future.

Positions held since graduation

  • Sep 2015- Professor, Departent of Chemical System Engineering, Graduate School of Engineering, University of Tokyo
  • Apr 2013- Director, International Research Cemter on Integrative Biomedical Systems (CIBiS), IIS, University of Tokyo
  • Nov 2008- Professor at IIS, University of Tokyo (Organs and Biosystems Engineering Lab.)
  • Nov 2003 to Oct 2008 Associate Professor at the Center for Disease Biology and Integrative Medicine (CDBIM),
    Graduate School of Medicine, University of Tokyo (Regenerative Medical Engineering Lab.)
  • Sep 2001- Oct 2008 Associate Professor at IIS, University of Tokyo (Organs and Biosystems Lab.)
  • Jul 1998- August, 1998 Lecturer at IIS, University of Tokyo
    (Environmental Chemical Engineering Lab. organized by Prof. M. Suzuki)
  • May 1997- April 1998 Visiting Scientist at the Department of Chemical Engineering, University of Rochester
    (Host was Prof. J. H. David Wu)
  • May 1990- Research Associate at IIS, University of Tokyo
    (Environmental Chemical Engineering Lab. organized by Prof. M. Suzuki)

Education

  • Doctor of Philosophy, University of Tokyo (1993). Major, Chemical Engineering;
    Thesis title, Study on the control of morphology and functional expression of anchorage-dependent mammalian cells.
  • Master of Engineering, University of Tokyo (1989). Major, Chemical Engineering;
    Thesis title, Kinetic study on the attachment and spreading of cultured mammalian cells.
  • Bachelor of Engineering, University of Tokyo (1987). Major, Chemical Engineering;
    Thesis title, Study on the secretion mechanism of alpha-hemolysin in E. coli cells.

Scientific awards

  • January, 2009: Publication award for 2008, FANUC FA and Robot Foundation Toshiki NIINO, Hiromichi NARUKE, Shunsuke OIZUMI, Yasuyuki Sakai, Hongyun HUANG (Institute of Industrial Science) fabrication of three-dimensional scaffolds for regeneration of high-metabolic-rate organs by selective laser sintering using water soluble leachable filler - Fabrication of porous bodies with fine flow channel network from biodegradable plastic - (Journal of the Japan Society for Precision Engineering, (73(11), 1246-1250, 2007) FANUC FA and Robot Foundation
  • December, 2006: Paper award of the Japanese Society for Alternatives to Animal Experiments, Development of a toxicity evaluation system for gaseous compounds using air-liquid interface culture of a human bronchial epithelial cell line, Calu-3, AATEX, 11, 59-67 (2005).
  • September, 2001: Publication Award of the Society for Bioscience and Bioengineering, Japan, Rapid and sensitive neurotoxicity test based on the morphological changes of PC12 cells with simple computer-assisted image analysis (J. Biosci. Bioneg., 90(1), 20-24 (2000)).
  • September, 1996: Young Investigators Award of the Society of Chemical Engineers, Japan, Large-scale preparation of porcine hepatocyte spheroids and their immobilization for bioartificial liver systems.

Professional activities

  • Jan 2001 - Japanese Society of Alternatives to Animal Experiments (JSAAE), administrator officer, vice president, chair of PR committee, chair of planning, permanent editorial board of AATEX journal, Chair of PR committee, WC6-2006 in Tokyo (World Congress on Alternatives and Animal Use for Life Sciences) etc.
  • April 2000 - Japanese Society of Artificial Organs (JSAO), Councilor, member of Information and PR committee, member of selection of councilors, member of future planning etc.
  • Oct 2004 - Society for Chemical Engineers, Japan (SCEJ), Member and chair of Medical Group, Division of Biotechnology, Organizing member of Kanto Branch, etc.
  • Oct 2006 - Japanese Society of Regenerative Medicine, Councilor
  • April 2007 – March 2010 Member of the technical roadmap committee (Risk evaluation and management of chemicals), Ministry of Economy, Trade and Industry (METI), Japan.
  • April 2005 – March 2007 Japanese Society of Therapeutic Engineering, Editorial Board of the Society Journal
  • Oct 1998 – May 2003 Japanese Society of Water Environment, member of the committee for planning, organizing member of Kanto Branch etc.