Tsuji and his colleagues have developed a new cell manipulation technology whereby organ germs are artificially recombined from single cells. This technology has the potential for application to artificial "tooth regeneration" and "hair regeneration".
This finding was announced in an Advanced Online Publication of the international scientific journal “Nature Methods” at 13:00hrs (Eastern US Time) on Feb. 18th, 2007. It is also due to appear in the March issue of the journal’s paper version.
The research outcome is expected to substantially advance the development of “organ replacement regenerative therapies”, and potentially as the next-generation regenerative therapies for replacing diseased or damaged organs with artificially engineered organs. Specifically, it will not only promote “tooth regenerative therapies”, whereby organ germs of artificially engineered teeth are transplanted into the oral cavity to grow “3rd generation teeth”, and “hair regenerative therapies” following hair loss, but is expected to evolve into a wide range of organ regeneration technologies for liver, kidneys and other organs.
Background to the research:
Regenerative therapies, the medical therapies of the 21st century, are now undergoing basic research and clinical application.
Current regenerative therapies have developed with a focus on “cell transplant therapy using stem cells”. In this process, stem cells that exist in vivo and ES (embryonic stem) cells produced by induced cell division from specific cells in vitro are transplanted in vivo.
The next-generation regenerative therapies will be “organ replacement regenerative therapies”, whereby diseased or damaged organs will be replaced with artificially engineered tissues and organs through cell manipulation in vitro. There are good prospects for the development of basic technology to this end.
At present, however, research and development are concentrating on reflux type or implanted artificial organs using in vivo materials, multi layering of cell sheets formed from single cell strains, and so on. There is no technology for creating artificial organs with a tissue structure made of multiple cell strains.
Outline of the research outcome:
In all organs, organ germs are first induced by the reciprocal action of epithelial cells and mesenchymal cells in the embryonic stage, after which organs consisting of multiple cell strains divide and grow through the continuous reciprocal action of these epithelial and mesenchymal cells.
The research group developed basic technology on the model of the tooth as an ectodermal organ. The aim of this was to reconstitute organ germs from simplified cells by manipulating cells in vitro and then to grow these artificial organ germs in vivo.
An important issue in this process is how to recombine simplified epithelial cells and mesenchymal cells via cell manipulation, and whether the reconstructed germs of artificial organs will grow normally in the targeted locus of the adult host.
The research group developed technology for simplifying and extracting epithelial cells and mesenchymal cells from tooth germs (organ germs of teeth) that exist in mouse embryos, then reconstituting the epithelial and mesenchymal cells separately in collagen gel in vitro under conditions of high density. The group succeeded in growing multiple teeth with the same tissue structure and periodontium as normal teeth, with “100% frequency”. They confirmed that this technology can also be applied to other ectodermal organs, i.e. hair follicles (whiskers), and that hairs (whiskers) can be grown from artificial hair follicle germs engineered from simplified epithelial and mesenchymal cells extracted from hair follicles.
Whether the germs of artificial organs will grow in the target locus of the adult host is the key to creating the “replacement regenerative therapies” of the future. Another major issue in this respect is whether nerves can be made to penetrate organs grown in this way, for the organs to fulfil their proper functions in vivo. Until now, however, there have hardly been any reports on the growth of artificial organs. The research group transplanted organ germs of artificial teeth into the extracted tooth cavity of an adult mouse. The result was that initial growth within the jawbone of the adult mouse was the same as for normal teeth, and it was proved, for the first time in the world, that blood vessels and nerves exist inside regenerated teeth grown in this way.
This research outcome not only establishes the technology for artificially engineering organ germs of teeth and hair through cell manipulation, but could also assist in developing technology for creating a wide range of organs, such as liver and kidneys. Specifically, it not only has the potential for “tooth regenerative therapies”, whereby organ germs of teeth are transplanted into the oral cavity to grow “3rd generation teeth and “hair regenerative therapies” following hair loss, but is also expected to usher in the development of the next-generation “organ replacement regenerative therapies” for replacing diseased or damaged organs with artificially engineered organs.