Research and Development Strategy for Future Embryonic Stem Cell-Based Therapy in Japan.

Akihiro Umezawa,Hidenori Akutsu,Yoji Sato,Shinji Kusakawa,Yoichi Matsubara,Kazuaki Nakamura,Mureo Kasahara,Rin Amagase,Takashi Igarashi

doi:10.31662/jmaj.2018-0029

Abstract

Herewith, we review an updated progress of regenerative medical products using human embryonic stem cells (ESCs) in Japan. Two groups from Kyoto University and the National Center for Child Health and Development (NCCHD) established a novel derivation/cultivation system of ESCs for potential application in translational and clinical research. At the first stage of ESC derivation, murine feeder cells have been used in line with Japanese guidelines on public health associated with the implementation of the xenograft. To avoid exposure of ESCs to animal products in culture media, a xeno-free cultivating system has been established. Twelve ESCs (KhES-1, KhES-2, KhES-3, KhES-4, KhES-5, SEES-1, SEES-2, SEES-3, SEES-4, SEES-5, SEES-6, and SEES-7) are now available under a clinically relevant platform for industrially and clinically applicable regenerative medical products. NCCHD submitted an investigative new drug application to the Pharmaceuticals and Medical Devices Agency (PMDA) for using ESC-based products in patients with hyperammonemia due to genetic defects on March 2018 under the Pharmaceutical Affairs Law (now revised to the Pharmaceuticals, Medical Devices, and Other Therapeutic Products Act). Currently, up to ten ESC-based products are being prepared for intractable and rare disorders in Japan.

Highlights

The derivation and utilization of human embryonic stem (ES) cells have the potential to contribute significantly to the development of medicine and biology, they require careful consideration given the bioethical issues involved, including the use of human embryos, which have the emerging potential of human life, and the fact that human ES cells have been derived by destroying human embryos and have the potential to differentiate into any type of human cell
Based on the “Report on the Human Embryo Research Focusing on Human Embryonic Stem Cells” (March 6, 2000, Subcommittee of Human Embryo Research, Bioethics Committee, Council for Science and Technology), “Basic Ideas on the Handling of Human Embryos” (July 23, 2004, Council for Science and Technology Policy) and “Desirable Production and Use of Human Somatic Cell Nuclear Transfer Embryos for Research Purposes (First Report)” (February 1, 2008, Bioethics and Biosafety Commission, Council for Science and Technology Policy), the Minister of Education, Culture, Sports, Science and Technology hereby establishes these Guidelines in an effort to secure the proper derivation and distribution of human ES cells, by providing for fundamental matters to be observed from bioethical viewpoints, so that human dignity may never be violated in such activities
(4) A second category deriving institute should, when providing the explanation set forth in paragraph (1), take appropriate measures to protect the personal information of the donors of unfertilized eggs, etc., and should deliver respectively the written explanation set forth in the preceding paragraph and a document indicating that said explanation has been provided (referred to as the “explanation certificate” in paragraph (1) of the Article) to the donors, etc. and copies thereof to the second category donor medical facility

Summary

Introduction

(3) A person who has been nominated by the head of a first category deriving institute pursuant to the provisions of the preceding paragraph should, when providing the explanation set forth in paragraph (1), give the explanation to the donors of human fertilized embryos in an easy-to-understand manner by presenting a written explanation containing the following matters: (i) The purpose and method of the derivation of human ES cells (ii) The fact that the human fertilized embryos will be destroyed in the derivation process and any other matters on the handling of the donated human fertilized embryos (iii) The expected utilization method of the human ES cells and the results thereof (iv) The fact that the conformity of the derivation plan with these Guidelines has been confirmed by the first category deriving institute, the first category donor medical facility and the State (v) The fact that the personal information of the donors of the human fertilized embryos will not be transferred to the first category deriving institute and any other concrete methods for protecting such personal information (vi) The fact that, because human fertilized embryos are donated free, the donors will receive no reward in the future (vii) In cases where there is a possibility that the human ES cells may be analyzed genetically, a statement to that effect and the fact that those genetic analyses will not identify specific individuals (viii) In cases where there is a possibility that germ cells will be produced from human ES cells, a statement to that effect and the fact that human embryos will not be produced using the said germ cells.

Results

Conclusion