Teeth, whiskers bioengineered

In a study some experts say largely confirms previous work, a Japanese team shows new teeth can develop in the adult mouse mouth

By | February 19, 2007

Japanese researchers have successfully reconstituted two bioengineered organs -- teeth and whiskers -- from individual cells in mice, according to a report out this week in Nature Methods. Instead of relying on pre-fabricated, cell-seeded organ scaffolds, as tissue engineers have in the past, this paper relies on cellular self-assembly, tissue engineer Vladimir Mironov from the Medical University of South Carolina, Charleston, told The Scientist. The study "imposes a new paradigm: We don't need to depend on chemical engineers and scaffolds," noted Mironov, who was not involved in the research. "I'm very excited about this paper." Teeth develop during embryogenesis via the interplay of epithelial and mesenchymal cells. During the study, Takashi Tsuji of Tokyo University of Science and colleagues recapitulated that process by isolating these cell types from embryonic mouse incisor tooth germ. The researchers dissociated the tissues into single cells and injected large numbers of each type separately into adjacent regions of a drop of collagen gel, creating a three-dimensional tooth germ culture. The team then either cultured the drops for two weeks, or implanted them into a mouse kidney after two days in culture. According to coauthor Yasuhiro Tomooka, director of the Tissue Engineering Research Center at Tokyo University of Science, the use of dissociated cells distinguishes this study from previous tooth bioengineering efforts. "Previously, the scientists collected fetal tissue and then recombined them and made [a] tooth," Tomooka told The Scientist. "In our study, we collected tissues and then dissociated [them] into single cells and then rebuilt the bioengineered germ." Histologic examination demonstrated that both the cultures and implants developed the multiple tissue types found in mature mouse teeth, including dentin, pulp, enamel, bone, vasculature, and the periodontal ligament. A similar approach was found to work for whiskers, which were regenerated from epithelia and mesenchyme derived from whisker follicles. Treatment of dissociated cells with an antibody against beta-1 integrin, which is expressed at the interface between both epithelia and mesenchyme, disrupted organogenesis, demonstrating tooth development relied on both cell types. Significantly, when the authors implanted the primordial tooth germ from either source into an empty tooth cavity -- the space created by removal of a tooth in an adult mouth -- the teeth could fully develop in their normal locations. "This result is [the] first description that a bioengineered organ can develop at the appropriate site for engraftment in adult animals," Tsuji wrote in a statement provided to The Scientist. Tsuji declined a request for comment. Yet others in the field of dental bioengineering question the novelty of the work. "This doesn't take us any further forward then where we already are," Paul Sharpe, professor of craniofacial biology at the Dental Institute, King's College London, told The Scientist. "I think the paper largely confirms what's been reported in the last couple of years," agreed Tony Smith, professor of oral biology at the University of Birmingham, UK, and editor of the Journal of Dental Research (which has published related work by Sharpe). "Possibly the only difference is they have shown the tooth develop within a bony crypt in the jaw," rather than elsewhere in the jaw, as Sharpe's team did, Smith noted. What the authors of the current study have not done, however, is demonstrate that these growing teeth can properly erupt from the gums, Smith added. They also provide little detail about how they achieved the shape of the tooth's crown or how well it is attached to the periodontal ligament, which both positions the tooth and protects it from breaking during chewing, Smith said. More to the point, the authors used embryonic cells, which are not available in adult humans. "One of the problems with reengineering an organ like a tooth is where you're going to get your cells from," Smith explained. "You either need cells that are already programmed to have a dental fate, or you need other cells that you then program to achieve a dental fate." Tomooka said he and his co-authors are now searching for adult murine cells that can replace the embryonic tissues used in this study. "The adult brain has stem cells making neurons. Maybe somewhere in your mouth we can find such cells." Indeed, he said he has a manuscript in preparation describing one possible candidate. "With high possibility there are such cells in the adult mouth," he said. Jeffrey M. Perkel mail@the-scientist.com Links within this article K. Nakao et al., "The development of a bioengineered organ germ method," Nature Methods, advance online publication, DOI:10.1038/nmeth1012 http://www.nature.com/nmeth/index.html A. Constans, "Body by science," The Scientist, Oct. 6, 2003. http://www.the-scientist.com/article/display/14154/ A. Constans, "Machining the body," The Scientist, May 9, 2005. http://www.the-scientist.com/article/display/15456/ Paul Sharpe http://www.kcl.ac.uk/depsta/crdebi/whoswho/PaulSharpe.htmlM B. Hu et al., "Bone marrow cells can give rise to ameloblast-like cells," J Dent Res, 85:416-21, 2006. http://www.the-scientist.com/pubmed/16632753 A. Ohazama et al., "Stem-cell-based tissue engineering of murine teeth," J Dent Res, 83:518-22, 2004. http://www.the-scientist.com/pubmed/15218039 B. Hu et al., "Tissue engineering of tooth crown, root, and periodontium," Tissue Engineering, 12:2069-75, 2006. http://www.the-scientist.com/pubmed/16968149 T. Powledge, "Neurogenesis happens in humans, too," The Scientist, February 15, 2007. http://www.the-scientist.com/news/home/52849

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