Laboratory of Stem Cell Therapy KAMIYA LAB
紙谷研究室
Principal Investigator:
Akihide Kamiya (Associate Professor）
Postdoctoral Fellow:
Hiromi Chikada
Research Assistant:
Kinuyo Ida

Establishment of Cell Therapies for severe liver diseases using
hepatic stem/progenitor cells
Keywords: Hepatic stem cell, iPS cell, Liver regeneration, Liver development
Background and Motivation
Liver is the central organ of metabolism and hepatocytes, the main cellular component of the adult liver, express many enzymes and factors playing acrucial role in mature liver functions. Infection of hepatitis viruses, overtake of alcohol, or several metabolic disorders induce chronic liver hepatitis,
liver fibrosis, and hepatocellular carcinomas. In this laboratory, we are going to establish new stem cell therapy for these severe liver diseases.
Using our purification methods and in vitro culture systems of hepatic stem/progenitor cells (HSPCs), we have several research plans.
1. Analyses of molecular mechanisms of proliferation and differentiation of HSPCs.
HSPCs have high proliferative ability and bi-potency for differentiation into both mature hepatocytes and cholangiocytes. However, HSPCs could not
be expanded with sustained bi-potency over a long period of time, suggesting that the present culture system is insufficient to maintain self-renewal
activity. We are going to search genes regulating stemness of HSPCs for establishment of the efficient culture system.
2. Differentiation of human pluripotent stem cells into HSPCs for stem cell therapy .
Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells contain multipotency to differentiate into specialized cells of the three primary
germ layers and can grow for a long time in vitro. These cells are very useful to regenerative medicine for several diseases. I have research plans toanalyze molecular mechanisms regulating proliferation and differentiation of HSPCs derived from human iPS cells.

Originality
Human hepatocytes are expensive and variable because these cells are derived human donor livers. Several research groups have developed theculture methods which induce differentiation of human ES and iPS cells directly into mature hepatocytes. However, in vitro expansion of mature
hepatocytes is very difficult. In my research plan, a lot of functional hepatocytes will be made using two step methods; (1) HSPCs, which contain highproliferative activity, are purified from fetal and adult livers or induced from human iPS cells. (2) After long-term culture for expansion, HSPCs areinduced to differentiate into functional hepatocytes in vitro.

Impact and Perspective
Liver is the central organ for detoxification of drugs. During drug development for diseases, many candidate compounds are stopped in pre-clinicalresearch because of their liver toxicity. Cultured hepatocytes with high-level of metabolic functions are required for cell therapy for liver diseases,
analyses of metabolism and toxicity during drug development, and artificial livers for the treatment of acute liver failure. For these purposes, we will
establish new culture methods for proliferation and differentiation of hepatic stem/progenitor cells.

■ For more information:www.utokai.ac.jp/tuiist/english/tt/announcement_kamiya.html■ CONTACT:
Akihide Kamiya, Ph.D.
Tokai University Institute of Innovative
Science and Technology
Medical Science Division
143 Shimokasuya, Isehara City,
Kanagawa 259-1193 JAPAN
Phone +81(0)463-93-1121 (Ext. 2783)
Fax+81(0)463-95-3522
Email kamiyaa@tokai-u.jp