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Development and Prospects of Organ Replacement Regenerative Therapy

Hirayama, Masatoshi MD; Oshima, Masamitsu DDS, PhD; Tsuji, Takashi PhD

doi: 10.1097/ICO.0b013e3182a18e6c

Abstract: Current approaches for the development of regenerative therapies have been influenced by our understanding of embryonic development, stem cell biology, and tissue engineering technology. The ultimate goal of regenerative therapy is to develop fully functioning bioengineered organs to replace lost or damaged organs that result from disease, injury, or aging. Almost all organs including ectodermal organs, such as teeth, hair, salivary glands, and lacrimal glands, arise from organ germs induced by reciprocal epithelial–mesenchymal interactions in the developing embryo. A novel concept to generate a bioengineered organ is to recreate organogenesis and thereby develop fully functioning bioengineered organs from the resulting bioengineered organ germ generated via 3-dimensional cell manipulation using immature stem cells in vitro. We have previously developed a bioengineering method for forming a 3-dimensional organ germ in the early developmental stages, termed the “bioengineered organ germ method.” Recently, we reported fully functioning bioengineered tooth replacements after transplantation of a bioengineered tooth germ or a mature tooth unit comprising the bioengineered tooth and periodontal tissues. This concept could be adopted to generate not only teeth but also bioengineered hair follicles, salivary glands, and lacrimal glands. These studies emphasize the potential for bioengineered organ replacement in future regenerative therapies. In this review, we will summarize the strategies and the recent progress of research and development for the establishment of organ replacement regenerative therapies.

*Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan;

Research Institute for Science and Technology, Tokyo University of Science, Chiba, Japan;

Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, Chiba, Japan; and

§Organ Technologies, Inc, Chiyoda-ku, Tokyo, Japan.

Reprints: Takashi Tsuji, Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan (e-mail:

This work was partially supported by Health and Labour Sciences Research Grants from the Ministry of Health, Labour, and Welfare (No. 21040101 to T.T.), a Grant-in-Aid for Scientific Research in Priority Areas (No. 50339131 to T.T.), a Grant-in-Aid for Scientific Research (A, to T.T.), and a Grant-in-Aid for Young Scientists (B, to M.O.) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. T. Tsuji is affiliated with Organ Technologies Inc. who supported the research. M. Hirayama received a Caterpillar Young Japan Investigator Grant from Caterpillar Japan Inc.

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