Stem Cell Research and Its Potential Influence on Dental Treatments

Stem cells are a key building block of human life. Advances in stem cell research are bringing American medicine closer and closer to the day when we will use cell-driven therapies to attack diseases or repair damaged body parts.

In some cases stem cells are being used in medical trials to reverse wear and tear injuries associated with aging, such as damage to a joint or a tooth. In others, doctors, dentists and medical researchers are using stem cells to regrow organs or bones. There has been extensive dental research along both of these tracks to understand how stem cells might help us one day repair damage to teeth and gums, or even regrow and replace the jaw bones of patients who have lost their jaw bone due to cancer, traumatic injury or developmental deformities.

“We don’t know when these treatments might be available for us to utilize, but we are committed to staying on the cutting edge of all research and offering new treatments to our patients whenever possible.”  

– Dr. Rusnak

Our goal at Rusnak Family Dentistry is to help you understand the latest trends in stem cell research and how those trends might one day lead to new therapies and treatment plans for patients.

Topics we will cover:

• An Introduction to Stem Cells

• Using Dental Stem Cells for Treatments and Repairs

• Re-Growing Bones and Tissues with Stem Cells

• Mapping out the Future of Stem Cells in Dentistry
  

An Introduction to Stem Cells

What makes stem cells a key part of life? Their ability to differentiate.

Human stem cells come in two types: embryonic and adult stem cells. Embryonic stem cells can become all cell types in the body, meaning they are pluripotent. Adult stem cells are generally thought to be limited in the ways they can differentiate (into muscle, nerve or bone, for example), though scientists are seeking to find ways to work with adult stem cells that can be differentiated into multiple types of tissues. This ability, which was first discovered in 2006, is called induced pluripotent stem cells.

These induced pluripotent cells are genetically engineered back to their embryonic state. Though research on these cells is less than a decade old, scientists have already begun using these newly-discovered cells in drug research. There is particular hope that the cells can help doctors who specialize in transplant medicine. Therapies that use induced pluripotent cells could help regrow damaged tissues around an organ that must be replaced and could also help reduce the risk of organs being rejected by the new host’s body.

Consider this example: Doctor’s must remove a portion of a patient’s jaw to treat a cancerous tumor. They wish to transplant new bone material into the hole created by the removal. To grow the bone, doctors and dentists might remove induced pluripotent stem cells from another portion of the patient’s body and reverse them back to their embryonic state, meaning those cells could become any human tissue. The cells are then activated as jaw bone cells. When the new piece of bone is implanted into the patient, there is a lower risk of rejection because the new bone fragment is a genetic match with the rest of the jaw. That’s because the new piece of bone and existing jaw grew from the DNA and stem cells of the patient.

This potential — the ability to grow new organs from the stem cells of a patient who needs a transplant, could radically alter medicine. Currently the need for transplanted organs far outweighs the supply. People spend months — and sometimes years — waiting for a transplant that matches their need. Many people die before receiving that transplant. If new therapies allow us to grow organs from a person’s own body, more organs would be available, and rejection risks would be far lower.

An important attribute of stem cells is that they can renew themselves through cell division, sometimes after long periods of lying dormant. In the gut and bone marrow, stem cells regularly divide to repair worn out or damaged tissues. In many organs, however, they divide only under special conditions.

We already use cancer cell lines to screen potential anti-tumor drugs or to test the safety of medications in laboratory settings.In time we hope cell-based therapies might allow us to repair damaged organs or replace destroyed ones, because the need for transplantable organs outweighs the available supply.

Before this can happen, we will need to show that stem cells can generate sufficient quantities of cells to make the desired tissue. The cells must then show they can survive in the recipient after transplant, function as needed for the remainder of the recipient’s life and avoid harming the recipient of the stem cells (even if the recipient is also the person who gave the stem cells). Scientists are studying how to avoid immune rejection (when a person’s immune system rejects the stem cells or organ that has been transplanted. This research has great potential, but technical hurdles – and years of research – remain.

Using Dental Stem Cells for Treatments and Repairs

Some of the most interesting stem cell research is being performed at Virginia Commonwealth University, where Dr. Rusnak, Dr. Adler, and Dr. Vinson all earned their doctor of dental surgery (D.D.S) degrees.

At VCU, work on stem cells involves very close collaboration between the School of Engineering and School of Dentistry. Dr. Zao Lin, a member of the VCU dental faculty, is exploring the role of stem cells in periodontal regeneration. Dr. Lin is focused on re-growing a number of damaged tissues, including the gingiva (gums), periodontal ligaments and cementum (the surface layer of teeth roots).

Dr. Lin hopes this research will eventually allow for new treatments of severe periodontal disease that improve upon existing options. Periodontal disease, also known as gum disease or gingivitis, appears as red or inflamed gums in its mildest forms and is currently irreversible. Severe periodontal disease can cause major damage to the gums, teeth and jawbone. According to the National Institutes of Health, periodontal disease is one of the leading causes of tooth loss.

Dr. Lin hopes his research might one day allow for guided tissue regeneration.

Stem cells could be injected into damaged areas of the mouth after a dental problem has been treated. Once the gum disease is reduced, stem cells could help regrow and reform the damaged tissues.

He is also studying the use of barrier membranes to support bone growth. Dr. Lin’s research is focused on the use of mesenchymal stem cells, which are generally extracted from bone marrow.

This research is being done in collaboration with the VCU School of Engineering, where Dr. Barbara Boyan, dean of the School of Engineering, and Dr. Zvi Schwartz, a dentist, biomedical engineer and associate dean, are working to help Dr. Lin isolate and identify microvesicles.

Microvesicles and their Role in Stem Cells

Microvesicles are small fragments of plasma membrane shed by almost all cell types. Dr. Lin hopes that by identifying the ribonucleic acid — RNA, a molecule that helps with the coding of genes — found in these microvesicles, he can identify the RNA sequences that tell a stem cell to differentiate into the different tissue types found in the human mouth (gingiva, bone and ligament, for example). Identifying the proper microvesicles would allow treatments to be targeted at specific parts of the mouth.

Researchers at VCU are also working to understand how the ability of stem cells to repair damage might be affected by the age and health of a patient. To date, most studies have been completed using stem cells from young, healthy subjects. But if researchers and clinicians hope to use treatments that rely on stem cells from dental patients, they will need to be sure that the cells perform as desired even if the patient is older or in poor health. It is currently not known if stem cells from older patients are any less effective at regrowing bone.

One interesting element of current research is seeking to understand how treating periodontal disease might help deal with other, seemingly unrelated health problems. This association raises the importance of treating gum disease as part of improving all aspects of a person’s health and well-being.

“As dentists, we have always recognized the positive relationship between one’s oral health and their overall health. New research is now emphasizing this relationship by highlighting the importance of proper periodontal care for patients.”

– Dr. Adler

The ultimate goal of periodontal therapy would be to regrow or regenerate damaged tissues. Most current therapies are focused on the repair of connective tissue. These treatments do not include work on the cementum — the top layer of the tooth’s root — or on the aveolar bone — the thickened ridge of bone that contains the tooth sockets. Studies conducted over the past 10 years have shown that when bone-marrow stem cells are implanted into damaged portions of the gum, they have successfully grown new cementum, which in turn creates an environment that helps the gums heal.

Re-Growing Bones and Tissues with Stem Cells

In some cases, implanting stem cells into the mouth to regrow damaged tissues may not be possible. If a patient has lost large quantities of bone, tissue or teeth, it may be necessary to grow the needed elements and implant them in the patient. This may be more difficult to achieve than implementing stem cells to repair tissues.

Despite the difficulties of growing new bones or tissues and safely implanting them in a patient, researchers at several universities have made exciting advances in recent years along those lines.

University of Michigan

Doctors at the University of Michigan School of Dentistry successfully regenerated a patient’s jawbone with the use of stem cells. The work was performed on a 45-year-old woman missing seven front teeth plus 75 percent of the bone that once supported them. The teeth and bone had been lost five years earlier after a trauma to the woman’s face. This injury left the patient with functional and cosmetic difficulties. The missing bone made it impossible to replace the missing teeth with dental implants.

Small gelatin sponges were seeded with stem cells and placed in the areas where small pieces of the jaw bone that were missing. Larger gaps were filled by phosphate scaffolds, which created a more rigid structure to support the area where bone would grow. Within four months the stem cells had regrown 80 percent of the missing jaw, allowing the team of dentists to proceed with traditional oral implants. When the procedures were completed, the woman again had a full set of teeth. The procedure was the first to successfully use stem cells to regrow bones damaged or lost in facial trauma. Further research is expected to build on the work done by the Michigan team.

University of California Los Angeles

Bone-growth research is also underway at the University of California Los Angeles under the direction of Dr. Benjamin Wu. Wu has a dental degree and a doctorate in materials engineering; he serves as the chairman of UCLA’s department of bioengineering.

The research at UCLA seeks to discover better ways to grow or regenerate bone and cartilage in many parts of the body. One of the most interesting discoveries to come from Wu’s lab is the identification of Nell1, a key growth factor that helps jumpstart the body’s own stem cells to repair lost or damaged bone and cartilage tissues. UCLA researchers hope that they can isolate Nell1 and use it to send signals to the stem cells already present in a patient’s muscles and bones (rather than introducing new stem cells or removing them from a patient and activating them outside of the body in a laboratory setting).

This discovery could have significant implications for treating trauma patients with significant musculoskeletal injuries and can also be used to treat or reactivate stem cells in aged populations with osteoporotic bone loss or cartilage loss from wear and tear and osteoarthritis. Most of the current treatments in this field focus on slowing or preventing bone loss, whereas these new treatments could help regrow bones and reverse past damage.

University of Southern California

This reactivation of stem cells is also being studied at the University of Southern California, where researchers are attempting to understand how the genetics involved in the teeth of rodents — such as mice or hamsters — might help us learn how to regrow damaged teeth in humans. The teeth of rodents never stop growing. That’s why rodents are almost always chewing on something; they must continually wear down teeth to avoid having those teeth grow too large. The researchers at USC hope to understand what genetic orders tell a rodents’ teeth to keep growing. Once that process is understood, it may be possible to use the information to tell human teeth to resume the growth that normally stops when we are children.

Mapping out the Future

Though a wide range of stem cell research projects are underway, treatments incorporating stem cells are not likely to be available in American dental offices for several years.

“Although the utilization of stem cell therapy is not on the immediate horizon at Rusnak Family Dentistry, we are excited about the increased research being done to better the lives of our patients.”

– Dr. Adler 

The federal Food and Drug Administration’s process of drug and treatment development is complex and is very time-consuming.

If animal studies show potential, researchers file an Investigational New Drug Application. Then, it moves to the three stages of human testing.

Three Phases of Human Testings

Phase I

To start, the studies are generally small, focusing on 20 to 80 healthy patients. During this phase of a clinical trial, treatments are studied to observe the most-common side effects and to understand how any drugs involved in the treatment are metabolized and secreted. The key emphasis of phase one is safety — researchers want to ensure the treatment is not going to harm patients.

Phase II

As the study progresses, it brings a larger number of participants into the process, and the focus now turns to examining whether or not the therapy will solve the problem it seeks to cure. Phase II studies are generally controlled trials, meaning about half of the patients will receive the drug or therapy, while half receive an inactive substance, known as a placebo. This allows researchers to see how much improvement patients receiving the drug experience, and then compare that improvement to patients who did not get the treatment. Safety continues to be examined, as this phase involves a larger patient population — up to 300 people.

Phase III

If the results from Phase II do not uncover safety problems, and if the treatment appears to be having a positive effect on patients, a clinical trial will proceed to the 3rd phase. Before treatments begin, researchers meet with regulators from the FDA. These meetings determine how large the Phase Trial needs to be; some studies have involved as many as 3,000 people. The focus in Phase III is studying different populations of people to determine the most effective dosage and drug schedule.

Though Phase III is generally the last part of a trial before seeking FDA approval of a drug, the agency may require post-approval studies so that researchers can continue to monitor for unnoticed side effects and work to refine the optimal dosage for drugs.

Filing a New Drug Application with the FDA

Following the conclusion of the three phases, researchers file a New Drug Application with the FDA. The administration has two months to decide if it will accept the application, and it then will spend about six months determining if the drug will win approval. Once that approval is granted, the drug or therapy can be made available to the general public.

This process takes several years, in large part because each phase of a clinical trial can run for a year, and sometimes longer. Researchers must find and enroll enough qualified patients for each phase of the study and ensure they set aside enough time to fully review a treatment’s effectiveness and side effects. Because of the complex nature of clinical trials, it is difficult to estimate when many of these new and novel treatment options might be available to the public. In many cases, researchers are entering unprecedented territory as they seek to regrow missing or badly damaged pieces of the mouth and jaw.

Though we do not know exactly when Rusnak patients might be able to benefit from these therapies, we wanted to take the time to inform you about the exciting research currently underway. It is our hope that in time these therapies will help improve quality of life for people with extensive dental treatment needs.