Adult Stem Cells Could Treat Tooth Loss

Pioneering techniques aiming to grow new teeth from a patient's own stem cells will be on display at the Royal Society's Summer Science Exhibition which opens to the public on 1 July 2014. Bioengineered stem cell teeth could challenge the use of artificial dental implants. Worldwide we spend more on dentistry than we do on many medical treatments. Everyone in the developed world will receive dental treatment at some point and it doesn't come cheap - current implants to replace broken or decayed teeth cost around £2000. Screwed directly into the jaw, they fail to reproduce the normal connection between teeth and bone and might work loose in less than 30 years. Scientists are developing an innovative procedure that would use cells from adult patients to grow full functioning teeth in situ. The treatment could be working in mice in 5 years according to exhibit leader Professor Paul Sharpe, Dickinson Professor of Craniofacial Biology at King's College London Dental Institute. Teeth can be grown from embryonic cells but Professor Sharpe says a treatment using only adult cells and growth-stimulating chemical factors that are already regulated for use in treatment, has a much better chance of ever making it to market. 'It's very easy to grow teeth from embryonic cells in a lab environment but if it's going to cost £50,000 per implant it will never make it into clinical use,' says Professor Sharpe. Embryonic cells are surrounded by ethical controversy and could not be collected in the numbers necessary for approved large scale treatment in patients. Adult cells are a more accessible option and, if the patient's own cells are used, they could also negate the need for a lifetime of immunosuppressant drugs to avoid rejection. 'We're focused on an end point for patients and to replace current implants, a stem cell therapy needs to be price competitive. Patients are not going to pay for a treatment that costs 10 times as much as an implant. Realistically they would probably pay for a treatment that costs twice or three times as much because a bioengineered tooth would last forever. But to reach that point we need to go back to basics using only growth factors which are already regulated, and we need to use accessible cells from adults - that's where the challenge lies'. To grow a new tooth requires two types of cell, epithelial cells and mesenchymal stem cells. One of these types of cells must send instructions to the other cell population to begin creating the different cell types and tissues needed in teeth. Professor Sharpe's team have already shown that epithelial cells collected from adult patients' gum tissues during routine dental surgery can respond to instructions from embryonic mesenchymal cells to growth of teeth. The team is now searching for a source of mesenchymal cells from adults that will trigger the same responses. One source might be stem cells in adult bone marrow or teeth themselves, but these cells lose their ability to produce other types of tissue after 24 hours in culture. Professor Sharpe is working with Dr Abigail Tucker to figure out how to reawaken the properties of the cells to grow diverse tissue and unlock their ability to grow new teeth. Dr Tucker studies the replacement of teeth in the animal kingdom. Sharks and snakes grow teeth on a conveyer belt, constantly replacing those that are broken or fall out. New teeth grow in the dental lamina - a tissue packed with stem cells which die off in humans as soon as adult teeth come through. Dr Tucker studies the signals from cells in the stem cell rich dental lamina, to see how they trigger the formation of new teeth in these animals. Her work on signalling might help Professor Sharpe replicate the signals and perhaps revive the potency of adult cells to grow new teeth. 'We've shown in the lab that you can use epithelial adult cells with tooth-inducing mesenchymal cells from embryos and we've shown that embryonic epithelial cells with mesenchymal adult cells can grow new teeth. Now we need to combine adult epithelial and adult mesenchymal cells. It's one of the last pieces of the puzzle'.

Tooth Stem Cells Aid Strokes

The team, from the University of Adelaide in Australia, publish their results in the journal Stem Cell Research & Therapy. Led by Dr. Kylie Ellis, of the university's Adelaide Research & Innovation (ARI), the researchers say interest in using dental pulp stem cells for post-stroke neurological recovery has been growing, following successful pre-clinical studies. "The reality is," says Dr. Ellis, "treatment options to the thousands of stroke patients every year are limited." She explains that the main available drug treatment has to be dispensed within hours of a stroke, but most people do not have access to the treatment within that window, as they sometimes do not seek help immediately after a stroke occurs. In the lab, the research team was able to show that stem cells taken from teeth can flourish and "form complex networks of brain-like cells." Though the cells did not grow into full neurons, the team believes with time and the right conditions, it will happen. Dr. Ellis adds: "Stem cells from teeth have great potential to grow into new brain or nerve cells, and this could potentially assist with treatments of brain disorders, such as stroke." Discovery could yield 'tailor-made brain therapy' Along with her colleagues, Dr. Ellis has been working on a model in the lab for treatment in humans. She notes that, in this research, she and her team discovered that teeth-derived stem cells developed into cells closely resembling neurons. She says they do this by creating an environment for the cells as close to the normal brain environment as they possibly can. She adds that "instead of becoming cells for teeth, they become brain cells." Dr. Ellis and her team say they would like to have the capability to use a patient's own stem cells for "tailor-made brain therapy that doesn't have the host rejection issues commonly associated with cell-based therapies." Additionally, the bonus in using this tailor-made therapy is that it could mean a treatment option is available "months or even years after the stroke has occurred," Dr. Ellis adds. And beyond stroke therapy, they say their work with dental pulp stem cells creates the potential for exploring other common brain disorders in the lab, possibly yielding other new treatments. "What we developed wasn't identical to normal neurons," says Dr. Ellis, "but the new cells shared very similar properties to neurons. They also formed complex networks and communicated through simple electrical activity, like you might see between cells in the developing brain." In other stem cell research news, Medical News Today recently reported on a breakthrough study, in which researchers created the first disease-specific embryonic stem cell line with two sets of chromosomes. They said their findings could yield patient-specific therapies for type 1 diabetes. Meanwhile, researchers from another study created the first stem cell model for bipolar disorder, which they say could lead to new treatments

Tooth Loss Linked to Depression and Anxiety

At the 43rd Annual Meeting & Exhibition of the American Association for Dental Research (AADR), held in conjunction with the 38th Annual Meeting of the Canadian Association for Dental Research, R. Constance Wiener, from West Virginia University, Morgantown, presented a research study titled "Association of Tooth Loss and Depression and Anxiety." Tooth loss from caries and periodontal disease is an outcome from complex, chronic conditions. Several biopsychosocial factors are involved, including accessing care. Individuals reporting dental anxiety may avoid dental care; and individuals with depression may be negligent in self-care. In this study, researchers examined a potential association of tooth loss with depression and anxiety. The Behavioral Risk Factor Surveillance System (BRFSS) Survey is a complex, telephone survey of the Centers for Disease Control and Prevention and state health departments. In this study, the researchers used the BRFSS 2010 data (451,075 respondents). Analysis involved frequency, Chi square analysis, and complex survey logistic regression. Participants eligibility included being 19 years or older, and having complete data on depression, anxiety and tooth loss. There were 76,292 eligible participants; and 13.4% of participants reported anxiety, 16.7% reported depression, and 5.7% reported total tooth loss. The sample was evenly distributed between males and females; there were 68.7% non-Hispanic whites, 12.7% non-Hispanic blacks, 12.5% Hispanics, and 6.8% other. In Chi-square analysis by tooth loss: depression, anxiety, and a combined category of depression or anxiety were significantly different in tooth loss verses participants without the conditions. At the conclusion of this national study, the researchers found that depression and anxiety are associated with tooth loss. Funding for this study was provided by the National Institutes of Health National Institute of General Medical Sciences of the, U54GM104942.

Smoking And Taste Alteration

In a recent study it was noted that tobacco's chemicals are already known to cause a loss of taste in smokers, as well as structural changes to the fungiform papillae of the tongue - where taste buds are found. What has been unknown is to what extent smokers' taste range is affected, whether it returns to normal upon quitting smoking and if so, how long that takes. Taste buds are largely responsible for conveying sweet, sour, bitter, salty and metallic sensations. According to the Centers for Disease Control and Prevention (CDC), the responsibilities of the taste system include:  Triggering digestive systems that change secretions of saliva, stomach acid and pancreatic juices  Enhancing feelings of pleasure and satiety when eating  Determining quality of foods and determining "good" tasting foods from "bad" ones, which could have potential toxins. To further investigate the changes in taste buds caused by smoking, Jacob and colleagues tested the ability of 451 study participants to recognize and rate intensity of the four basic tastes - sweet, sour, bitter and salty. Tobacco product accumulation could impede taste bud regeneration Smokers may not be able to fully taste the bitterness of coffee, researchers say. Dividing the participants into three groups (smokers, non-smokers and former smokers), the team conducted the voluntary tests during three separate and consecutive "World No-Tobacco Days." A person's ability to recognize salty, sweet or sour tastes was not influenced by smoking status, the researchers say. However, smoking status did affect their ability to taste the bitterness in caffeine. While bitter receptors in the tongue are normally able to detect this sensation in even low concentrations, nearly 20% of smokers were not able to correctly identify the taste. Of the former smokers, 26.5% were not able to identify the taste, while only 13.4% of the non-smokers were unable to correctly identify the bitter samples. Speaking about their findings, Jacob says: "We consider that the perception of bitter taste should be examined more closely, both as a tool for smoking cessation or for preventing smoking initiation. More generally, it should be worthwhile to consider the role of chemosensory perceptions in smoking behavior." The team believes the accumulation of some tobacco products in the body could impede taste buds regenerating, which could still affect a person's ability to recognize certain tastes after they have quit smoking. In the world of taste bud studies, recent research has reported on a digital taste simulator that can produce the four main elements of taste. Researchers say it could one day be used to improve or regenerate sense of taste in cancer patients whose taste buds have been impaired by chemotherapy.

Premie's And Their Teeth

Our knowledge about premature children, and their physical and mental development as they grow up, is constantly growing. In recent years several studies of children's dental health have been published by researchers at the Faculty of Odontology in Malmö. Liselotte Paulsson-Björnsson, a specialist in orthodontics, has studied 80 children born before week 33 of pregnancy. "We have examined how their teeth are developing and, among other things, we've looked at their bites. We've also checked their need for orthodontic adjustments and found that it is greater than in the control group, children born at full term," she says. The children participating in the various studies were born in the mid 1990s and were examined when they developed their first permanent teeth at the age of eight to ten. The first permanent teeth are the front teeth in the upper and lower jaw and the so-called six-year molars, the first big molars. The results show that the teeth of premature children were up to ten percent smaller compared with the control group. The earlier the children were born the smaller their teeth were. "When we examined the children we also saw that their teeth were farther apart," says Liselotte Paulsson-Björnsson, who stresses that having small teeth as such is not a serious problem, but it can be aesthetically problematic to have large gaps between your teeth. "But these problems can be addressed. We can move teeth if the gaps between them are too large, and there is also good material to extend teeth if they're too small." Disturbances in the teeth's mineralization phase can also lead to spots on the front teeth, but this is also a problem that can be dealt with using cosmetic dental treatments. Liselotte Paulsson-Björnsson is now planning new studies to follow these children into their teens. Among other things, she will be studying whether all permanent teeth are affected in terms of size, or only the ones that are formed in connection with birth. She also wants to study the children's quality of life in relation to their dental status. "But as care of premature children is under constant development, it's not possible to automatically transfer my findings to children being born prematurely now," she says

New Gel Causes The Body To Form Teeth

A bit of pressure from a new shrinking, sponge-like gel is all it takes to turn transplanted unspecialized cells into cells that lay down minerals and begin to form teeth. The bioinspired gel material could one day help repair or replace damaged organs, such as teeth and bone, and possibly other organs as well, scientists from the Wyss Institute for Biologically Inspired Engineering at Harvard University, Harvard School of Engineering and Applied Sciences (SEAS), and Boston Children's Hospital report recently in Advanced Materials. "Tissue engineers have long raised the idea of using synthetic materials to mimic the inductive power of the embryo," said Don Ingber, M.D., Ph.D., Founding Director of the Wyss Institute, Judah Folkman Professor of Vascular Biology at Harvard Medical School, Professor of Bioengineering at SEAS, and senior author of the study. "We're excited about this work because it shows that it really is possible." Embryonic tissues have the power to drive cells and tissues to specialize and form organs. To do that, they employ biomolecules called growth factors to stimulate growth; gene-activating chemicals that cause the cells to specialize, and mechanical forces that modulate cell responses to these other factors. But so far tissue engineers who want to build organs in the laboratory have employed only two of the three strategies - growth factors and gene-activating chemicals. Perhaps as a result, they have not yet succeeded in producing complex three-dimensional tissues. A few years ago, Ingber and Tadanori Mammoto, M.D., Ph.D., Instructor in Surgery at Boston Children's Hospital and Harvard Medical School, investigated a process called mesenchymal condensation that embryos use to begin forming a variety of organs, including teeth, cartilage, bone, muscle, tendon, and kidney. In mesenchymal condensation, two adjacent tissue layers - loosely packed connective-tissue cells called mesenchyme and sheet-like tissue called an epithelium that covers it - exchange biochemical signals. This exchange causes the mesenchymal cells to squeeze themselves tightly into a small knot directly below where the new organ will form. By examining tissues isolated from the jaws of embryonic mice, Mammoto and Ingber showed that when the compressed mesenchymal cells turn on genes that stimulate them to generate whole teeth composed of mineralized tissues, including dentin and enamel. Inspired by this embryonic induction mechanism, Ingber and Basma Hashmi, a Ph.D. candidate at SEAS who is the lead author of the current paper, set out to develop a way to engineer artificial teeth by creating a tissue-friendly material that accomplishes the same goal. Specifically, they wanted a porous sponge-like gel that could be impregnated with mesenchymal cells, then, when implanted into the body, induced to shrink in 3D to physically compact the cells inside it. To develop such a material, Ingber and Hashmi teamed up with researchers led by Joanna Aizenberg, Ph.D., a Wyss Institute Core Faculty member who leads the Institute's Adaptive Materials Technologies platform. Aizenberg is the Amy Smith Berylson Professor of Materials Science at SEAS and Professor of Chemistry and Chemical Biology at Harvard University. They chemically modified a special gel-forming polymer called PNIPAAm that scientists have used to deliver drugs to the body's tissues. PNIPAAm gels have an unusual property: they contract abruptly when they warm. But they do this at a lukewarm temperature, whereas the researchers wanted them to shrink specifically at 37°C - body temperature - so that they'd squeeze their contents as soon as they were injected into the body. Hashmi worked with Lauren Zarzar, Ph.D., a former SEAS graduate student who's now a postdoctoral associate at Massachusetts Institute of Technology, for more than a year, modifying PNIPAAm and testing the resulting materials. Ultimately, they developed a polymer that forms a tissue-friendly gel with two key properties: cells stick to it, and it compresses abruptly when warmed to body temperature. As an initial test, Hashmi implanted mesenchymal cells in the gel and warmed it in the lab. Sure enough, when the temperature reached 37°C, the gel shrank within 15 minutes, causing the cells inside the gel to round up, shrink, and pack tightly together. "The reason that's cool is that the cells are alive," Hashmi said. "Usually when this happens, cells are dead or dying." Not only were they alive - they activated three genes that drive tooth formation. To see if the shrinking gel also worked its magic in the body, Hashmi worked with Mammoto to load mesenchymal cells into the gel, then implant the gel beneath the mouse kidney capsule - a tissue that is well supplied with blood and often used for transplantation experiments. The implanted cells not only expressed tooth-development genes - they laid down calcium and minerals, just as mesenchymal cells do in the body as they begin to form teeth. "They were in full-throttle tooth-development mode," Hashmi said. In the embryo, mesenchymal cells can't build teeth alone - they need to be combined with cells that form the epithelium. In the future, the scientists plan to test whether the shrinking gel can stimulate both tissues to generate an entire functional tooth.

"Big Tooth" Is Watching You !

Researchers at the National University of Taiwan have developed a “smart” tooth device that monitors an individual ‘s oral habits by recording movement of the jaw and generating data that is fed to a computer via the tooth’s sensor , then paired with an oral action . The device can be used as a detachable fake tooth or inserted in a crown , allowing doctors to track chewing , drinking , eating , coughing and even smoking – and (hopefully) allow them help treating a wide range of problems . In testing the device , the researchers asked 8 volunteers to perform 30 – second tasks such as chewing gum , reading aloud , drinking a bottle of water and coughing . The device was able to determine what action each volunteer performed with 94% accuracy . Because the mouth is “an opening into human health” , the researchers contend the device has the potential to enhance existing healthcare monitoring applications such as dietary tracking.