Polymer scaffolds guide stem cells growth into customized sizes and shapes.

It may be hard to remember what it was like to lose a tooth as a child, but many adults get an unpleasant reminder as they age when their teeth begin to fall out (even those who don’t play hockey) and must consider dentures or dental implants. For years, researchers have investigated stem cells in an effort to grow teeth made for a person’s own cells. Toward this end, endodontics professor Dr. Peter Murray and colleagues from the College of Dental Medicine at Nova Southeastern University (NSU) have developed methods to control adult stem cell growth toward generating dental tissue and “real” replacement teeth.

The NSU researchers’ approach is to extract stem cells from oral tissue, such as inside a tooth itself, or from bone marrow. After being harvested, the cells are mounted to a polymer scaffold in the shape of the desired tooth. The polymer is the same material used in bioreabsorable sutures, so the scaffold eventually dissolves away. Teeth can be grown separately then inserted into a patient’s mouth or the stem cells can be grown within the mouth reaching a full-sized tooth within a few months.

So far, teeth have been regenerated in mice and monkeys, and clinical trials with humans are underway, but whether the technology can generate teeth that are nourished by the blood and have full sensations remains to be seen. Teeth present a unique challenge for researchers because the stem cells must be stimulated to grow the right balance of hard tissue, dentin and enamel, while producing the correct size and shape.

As Dr. Murray explains it, humans already have two sets of teeth, baby and adult sets, over the course of their lifetimes, so “All we are trying to do is copy nature and give the person the third option to re-grow their teeth.” Not only could this be important for replacing lost teeth, but it could become a standard treatment when extreme orthodontics is necessitated. And if the tooth is malformed or fails, it can be extracted and a new one put into place.

To date, the NSU researchers have received about $1.7 million in grants for their dental stem cell research.

Dr. Murray believes that if they can demonstrate control over tooth re-growth and prove that the technology is safe, these teeth will be the first to see widespread adoption in the US. He also reports that interest has been high from the public and even fellow dentists, as evidenced by the recent selling out of his “Regenerative Endodontic Procedures” presentation at the American Dental Association conference in Las Vegas.

You can check out a news piece about NSU’s research here.

Just as developments in embryonic stem cell research launched umbilical cord banks, the promise that dental stem cell therapy holds has led to the rise of tooth banks, such as BioEden, StemSave, and Store-A-Tooth (StemSave, for instance, charges $2,430 to store a child’s tooth for 20 years.) Stem cell therapies are being actively used to repair bone damage, facial bones, and even organs like a heart, but skeptics continue to scoff at the potential of stem cells, oft citing nightmare scenarios or runaway tissue growth. Furthermore, research progress is often clouded by the politics surrounding embryonic stem cell research.

But the one therapy that could silence the naysayers is tooth regeneration.

The statistics on tooth loss are a bit staggering: 7 out of 10 adults age 35 to 44 have lost at least one tooth and a quarter of those aged 65 or older (or about 20 million people) have lost all their permanent teeth. Additionally, side effects from medications can effect oral health, such as changing properties of the saliva that helps fight bacterial growth. And increased tooth loss leads to poor dietary habits even among dentists, according to a recent study, which leads to secondary health effects. Add to this high sugar diets contributing to the obesity epidemic and increasing cases of periodontal disease due to neglect and you can see that the market for tooth replacement is enormous and expected to grow.

Having a full set of functional teeth is increasingly important as an aging population seeks to maintain an active lifestyle. And the growth of social media has led to people’s faces being plastered all over Facebook, Twitter, and YouTube. So how your teeth look is more important than ever, especially with more people carrying high quality cameras built into their mobile devices.

Dentists are at the front line of the increased demand for perfect teeth. A 2009 nationwide survey by NSU revealed that 96% of the dentists polled expected stem cell regeneration to dominate the future of dentistry. Additionally, more than half predicted that the technology would be available within the next decade.

In mice, stem cells grew into a tooth (in green) that had similar properties to natural teeth.

Research into using stem cells to regrow new teeth has been around for at least 10 years. In 2002, Professor Paul Sharpe at the Dental Institute of King’s College in London received a $500,000 Wellcome Trust grant to translate tooth regrowth with stem cells in mice into regenerative dentistry for humans. A company was formed, Odontis, and in 2010 seemed ready to launch its BioTooth technology, but has since fallen off the radar and had its website shut down possibly suffering the same fate that led to Geron Corporation abandoning stem cell research last year. Researchers from Tokyo University in 2009 reported success with implantation of stem cell tooth germs in mice which grew into fully functional teeth within a few months. Scaffolds were also successfully used to regrow anatomically correct teeth in nine weeks by researchers at Colombia University Medical Center.

Although the promise of stem cell therapies remains to be realized, there’s little doubt that researchers at NSU and around the world will continue in their efforts to use stem cells for regenerative medicine.

Dr. Murray remains optimistic: “When dental stem cell therapies become routine it will be historic, and the most fantastic time to practice as a dentist.”

[Media: Sun Sentinel]

[Sources: ABC, BBC, DentalAegis, Ivanhoe, PopSci, Sun Sentinel]

A homegrown bladder (Photo courtesy of BBC)

This research isn’t something that might happen in the distant future.  It’s being used today to grow fresh organs, open up new ways to study disease and the immune system, and reduce the need for organ transplants. Organ-farming laboratories are popping up across the planet, and showing impressive results. Here we look at the state of the union of a rapidly advancing field called tissue engineering: what’s been accomplished so far, and what’s right around the corner.

Patients who undergo organ transplants require loads of toxic drugs to suppress their immune systems; otherwise their body might reject the organ. But tissue engineering could make organ transplants a thing of the past. By using a patient’s cells to grow new types of tissue in the lab, researchers are finding new ways to custom-engineer you new body parts by using your own cells.

At the cutting edge of organ engineering is Tengion, a clinical-stage biotech company based outside of Philadelphia. Their most successful research to date led to the creation of the Neo-Bladder. Tengion takes some of your cells and grows them in culture for five to seven weeks around a biodegradable scaffold. When the organ is ready, it can be transplanted without the need to suppress the patient’s immune system (because the organ was grown from the patient’s own cells, it carries no risk of rejection). Once the organ is in, the scaffold degrades and the bladder adapts to its new (old) home.

The Tengion Neo-Bladder is in Phase II testing, meaning that they have already implanted the organ into individuals and studied how the body adapts to it.  After 5 years, the company was able to show that the homegrown organs are safe and effective, capable of treating the bladder effects of spina bifida (a neural tube defect that effects bladder function, among other things). After another round of Phase II trials, Tengion will move on to Phase III testing; after that, the Neo-Bladder should be approved and be made commercially available.

Atala wants to grow you an organ

Tengion’s Neo-bladder is nearing the completion of its clinical trials, but they weren’t the first to grow one. If anyone on Earth deserves the job title “Organ Farmer,” it’s Dr. Anthony Atala. He and his research team at Wake Forest University Medical Center pioneered the world’s first lab-grown bladder, and they remain at the forefront of the organ-growing field (Atala is also the chairman of Tengion’s scientific advisory board). Wake Forest is the world’s largest regenerative medicine research center, and their current research is growing 22 different types of tissue: heart valves, muscle cells, arteries, and even fingers.

So how many different types of human organs have been grown and transplanted? The lab-grown bladders are among the only transplants of an entire organ, but a wide variety of partial organ transplants have taken place. Skin cells are regularly grown in culture and grafted onto patients’ bodies. A graft was grown from a patient’s trachea cells and transplanted to replace part of her airway that had degraded due to disease. Cartilage has been grown and transplanted into a patient’s knee.

A number of technologies are under development but have yet to be transplanted into human bodies. Recently, Dr. Nicholas Kotov and his lab at the University of Michigan have engineered artificial bone marrow, a task that was previously doomed to failure. Kotov and his colleagues realized that in the body, stem cell differentiation relies on chemical signals in three dimensions (whereas in a petri dish, it takes place in two dimensions). This insight led to a new methodology that more closely replicated the natural environment of stem cell differentiation in bone marrow tissue. The resultant homegrown marrow grew and divided normally, even releasing antibodies in fight off an introduced influenza strain. It can be used to study the role of bone marrow in fighting disease within the body, as well as creating a “bioreactor”: harnessing the artificial marrow within a device to grow cells and tissues.

Tengion is pretty busy these days as well. Their new website lists a variety of new applications on the horizon, including a Neo-Kidney augment, artery replacements (including in the heart), and variations on their bladder technique to replace cancerous organs. Their company pipeline gives a general idea of the relative stages of each project.

A number of initiatives are under way to create an artificial pancreas, which would revolutionize the way we treat diabetes. By providing diabetics with a healthy pancreas, doctors could restore their natural control of blood glucose by giving them an endogenous source of insulin. Anyone with experience of diabetes knows the difficulty of manually monitoring and controlling your sugar levels, not to mention regularly injecting insulin. A lab-grown pancreas replacement would be an incredible benefit to the 23.6 million individuals in America alone who suffer from diabetes.

The Minnesota rat heart

As we previously reported, researchers at the University of Minnesota grew an entire rat heart in a laboratory last year. Their next goal is to grow a pig heart, a significant milestone towards growing a human heart due to their similar structure. Researchers hope to combine the scaffold of a pig heart with human cardiac tissue to grow a hybrid heart suitable for transplant.

Another exciting frontier is the field of printable tissue and organs, which is just what it sounds like. Inkjet cartidges are cleaned out and loaded with a mixture of live human cells and “smart gel.” Then, layer by layer, the cells are printed atop one another until a 3D organ is constructed. Just as a normal printer can deposit different colored ink, organ printing allows scientists to specify where to place different cell types. Organ printing has already created beating cardiac cells, and could soon produce organs that are viable for transplant. But unlike other 3D printers, I wouldn’t want this one in my living room.

The hottest areas in tissue growth are the types hardest to make: nerve, liver, kidney, heart and pancreas cells.  But these are precisely where Alata and Tengion are heading, pushing the industry into fresh territory. Coupled with new regenerative treatments like Cook biotech’s foams and stem-cell organ patching, tissue engineering will be keeping our organs young and healthy in the years to come.

Merely a decade ago, tissue engineering was still a new field that struggled to find funding and support. Today, thousands of scientists worldwide are coordinating efforts to reach new breakthroughs, and the demonstrated potential of these methods has helped bring in investors. That should keep the organ growing field moving forward in the future months and years, and we’ll be covering new advances as they emerge.

Check out this Wired Science video that tours around Atala’s lab: