By the time kids begin school most have learned that if they lose any of their new “permanent” teeth, those teeth will be lost forever. But did you know that some mammals -- mice, for instance -- have teeth that grow continuously? In Greek mythology, sowing the teeth of a fierce dragon caused fully armed warriors to spring forth and fight. Today it’s no myth to say that studies of the much meeker mouse might guide researchers to a more constructive harvest that benefits humans. Lessons learned about where, when and how teeth grow throughout life in mice may lead to strategies for re-growing teeth and treating or preventing human developmental anomalies that impact the face and dentition. These craniofacial anomalies, the best known of which are cleft lip and palate, are among the most common of all birth defects. Teeth recently have earned a starring role in the field of regenerative medicine, and at UCSF, Ophir Klein, MD, PhD, is a leading light. His lab is a beacon for promising postdoctoral fellows who want to explore how stem cells generate new teeth and how development goes awry in craniofacial disorders. Klein, who received a New Innovator Award from National Institutes of Health Director Francis S. Collins, MD, PhD, in September, also is funded by a major grant from the California Institute for Regenerative Medicine. This $3 million state grant funds a research proposal titled “Laying the Groundwork for Building a Tooth: Analysis of Dental Epithelial Stem Cells.”
A Proving Ground for Regenerative MedicineHumans and animals possess very small, self-renewing populations of stem cells. These vary in potential and potency, depending on developmental stage. At one extreme are embryonic stem cells, obtainable just a few cell divisions after sperm fertilizes egg. These cells can give rise to virtually any cell type in the body. Other stem cells are organ or tissue specific. Stem cells are rare. The vast majority of human cells are specialized and mature and they have no stem cell capabilities whatsoever. “We don’t know if these particular stem cells in mice also exist in humans,” Klein says. “There are reasons to think that some of them might. But what we really want to understand are the mechanisms by which stem cells can contribute to dental renewal.”
In August 2009, Klein became the director of the Craniofacial and Mesenchymal Biology (CMB) Program at UCSF. “CMB is a relatively new program that we are trying to build,” Klein says. “Our goal is to have a translational program that spans basic research similar to my own, and that extends to clinical work.” “Probably half of the basic research people in my lab are focused on trying to understand the genes and cellular behaviors that underlie the continuous growth of the incisor in the mouse. The rest investigate the role of different growth-factor signaling pathways in the development of structures within the embryo.” Klein wants to use stem cells to grow new teeth. He views teeth as a convenient starting point and proving ground for all of regenerative medicine. Teeth and the oral cavity are very accessible in comparison to the large, vital organs, yet what Klein learns about teeth is bound to apply to growing these other tissues. “There are a lot of sophisticated aspects of tooth function,” he says, “but you might not have to form a tooth as perfectly as a heart or kidney in order for it to function adequately.” Still, growing teeth is an ambitious project. Klein is optimistic about success, but it will require many years to achieve, he says.