StemCell Therapy

April 2012, Volume 8, Issue 4 Published by AEGIS Communications

By Peter E. Murray, BSc(Hons), PhD | Pamela C. Yelick, PhD | Thomas G.H. Diekwisch, DMD, PhD, PhD

Dentists are enthusiastic about using stem cell therapies and are willing to get training to deliver stem cells to give patients replacement teeth and gums. The Regenerative Endodontic Procedures presentation I made at the American Dental Association conference in Las Vegas was sold out. Every day I am getting letters, e-mails, and telephone calls from people asking me to grow teeth for themselves or their child. A high demand exists for dentists to give their patients dental stem cell therapies. Dentists appear optimistic that stem cells will allow them to deliver more miraculous therapies that will benefit their patients and improve their quality of life.

Some dentists are collecting baby teeth to be used as a source of stem cells, through stem cell banking companies such as BioEden, StemSave, and Store-A-Tooth. The hope is that these dental stem cells could be used to heal the patients when they need it in the future. These services were unthinkable only a few years ago. The next stem cell advance I expect is the availability of regenerative dental kits, which will give dentists the ability to deliver stem cell therapies in their own office. The delivery of stem cell therapies by the dentist is complicated, and these kits will simplify the process and make the treatment more affordable.

Dental researchers have learned how to revitalize tissue in necrotic teeth and regenerate teeth and also grow teeth in mice; it is just a matter of time and money before these therapies replace implants and dentures. The recent face transplants and jaw replacements have taught us how to successfully reconnect tissues to nerves and the blood supply. These advances have allowed surgeons to make someone who was a victim of facial trauma or cancer whole and healthy again. X-ray imaging technologies such as cone beam and micro-CT will add a new dimension to tooth and tissue replacement by allowing the dentist to design replacement body parts to be regenerated by dental stem cells. The goal of the dental stem cell researcher is to give the dentist the power to make every patient whole and healthy. When dental stem cell therapies become routine it will be historic, and the most fantastic time to practice as a dentist.

Dental stem cells are adult stem cells present in both baby (deciduous) teeth, and adult teeth. The stem cells consist of dental mesenchymal stem cells and dental epithelial cells. Dental epithelial cells give rise to enamel, while dental mesenchymal stem cells give rise to all of the other tissues of the tooth, including pulp, dentin, cementum, periodontal ligament, and surrounding alveolar bone. Mesenchymal cells are derived from ectomesenchymal neural crest cells, which provide teeth with their unique characteristics as compared to mesodermal cell-derived bone-forming stem cells. Dental stem cells have been characterized from a variety of tooth tissues, including the pulp, periodontal ligament tissues, specialized immature tooth-rootderived stem cells of the papilla (SCAP), and the surrounding alveolar bone. Although erupted teeth no longer have enamel-progenitor stem cells present, very immature unerupted teeth have soft enamel organ tissues that are rich in enamel-forming epithelial progenitor cells and blood vessels.

Harvested dental stem cell populations are quite heterogeneous, which can be both an asset and a liability. There is no reliable way to efficiently generate large numbers of pure dental stem cell populations in culture at the present time, and in fact, these populations change over time in culture, indicating that they prefer not to exist as homogeneous stem cell populations.

Dental stem cells are a valuable autologous adult stem cell source, meaning that they can be used in the same individual without the danger of an immune rejection response, with potential use for regenerative medicine approaches. They are multipotent, meaning that they can give rise to a limited number of tissue types, including cartilage, bone, adipose tissue, neural, and tooth tissues. The ability to harvest cells from extracted wisdom teeth and supernumerary teeth that would otherwise be discarded as waste makes these tissues unique and valuable stem cell sources. The successful demonstration that harvested dental stem cells can be cryopreserved for extended periods of time and subsequently thawed and differentiated into a variety of tissues, including bone, dentin, nerve, and adipose tissues, has fueled the tooth-banking industry for eventual use of cryopreserved dental stem cells in regenerative medicine applications.

What are the potential clinically relevant applications for dental stem cells? These cells are now being tested for their potential use in a variety of clinical applications, ranging from use as immuno-modulatory agents and as regenerative stem cells that can facilitate regeneration of cardiac tissues, bone, and even neuronal tissues. Human mesenchymal stem cells, including dental stem cells, have been tested for spinal cord regeneration in animal models. While a few dental stem cell therapies have been conducted in humans, the vast majority of these studies have been performed in animal models, making their utility in humans uncertain at the present time. One approach that holds great promise is to generate induced stem cells (iSCs) from harvested human dental stem cells. This approach, which reprograms dental stem cells into an embryonic state, thereby expanding their potential to differentiate into a much wider range of tissue types, has tremendous appeal for autologous tissue engineering applications. Barriers to this approach include the fact that iSC reprogramming efficiency is extremely low at the present time, and largely relies on the use of retroviruses, which have carcinogenic potential. Another useful application is to study dental stem cells harvested from individuals exhibiting a variety of craniofacial skeletal and dental syndromes in order to increase our understanding of the molecular nature of diseases ranging from cleidocranial dysplasia syndrome (CCD), Sensenbrenner syndrome, and Treacher-Collins syndrome. In this way, targeted therapies may eventually be devised to treat and/or prevent some of these diseases.

One of the most promising uses for harvested dental stem cells is for applications in regenerative dentistry. Dental tissue-engineering approaches combining dental stem cells, biodegradable and biocompatible scaffolds, cell sheet technologies, and exogenous growth factors are being used to devise methods to reliably regenerate dental tissues including pulp, periodontal tissues, alveolar bone, dentin, enamel, and salivary glands. Although not currently available, these approaches may one day be used as biological alternatives to the synthetic materials currently used.

Teeth are unique in that they provide readily accessible sources of adult stem cells for tissue regeneration and repair. Similar to other organs in the human body, adult teeth and their surrounding tissues contain mixed populations of cells, including differentiated cells as well as a number of adult stem cells (progenitor cells). While other organs in the body are essential throughout life, teeth are replaced at least once when the deciduous dentition is lost in favor of the permanent dentition. These deciduous teeth provide an easily accessible source of stem cells. Wisdom teeth form a second readily available source of stem cells in adolescent jaws. Stem cells from teeth may not only be useful for the regeneration of dental tissues but also contribute to the regeneration of non-dental organs, such as the liver or heart.

Studies in our laboratory have demonstrated that periodontal stem cells are capable of completely renewing a periodontal ligament. Studies in humans using stem cells to aid periodontal therapy are currently underway, outside of the United States. Alveolar bone regeneration is an area that could still significantly benefit from innovative stem cell and tissue regeneration approaches.

Much progress has been made indicating that pulp stem cells are capable of forming pulp-like tissues and some of these approaches are useful to rescue pulp tissue. Clinically, replacement of an entire pulp is still challenging because of limited access of regenerated tissues to blood vessels and nutrients at the root apex.

Stem cells in conjunction with growth factors have resulted in successful new bone formation and regeneration in small defects. Future advances in stem cell research will thus focus on the regeneration of larger defects and the regeneration of functional bone.

Scientifically, the regeneration of whole teeth de novo remains the most attractive challenge in dental tissue regeneration. Coaxing dental stem cells into initiating developmental cascades to form complex tooth organs with enamel, dentin, and roots would be both scientifically and clinically attractive. So far, progress has been based on the ability of tooth germ-derived tissues to self-organize and reassemble into a developing tooth organ. Another group of scientists has advanced the field by identifying factors responsible for supernumerary teeth, prompting the hope that these factors might reveal the inductive code required to trigger new tooth formation.

Peter E. Murray, BSc(Hons), PhD | Dr. Murray is a postgraduate research administrator and professor in the Department of Endodontics, College of Dental Medicine, Nova Southeastern University.

Pamela C. Yelick, PhD | Dr. Yelick is a professor in the Department of Oral and Maxillofacial Pathology, in the Sackler Genetics and Cell Molecular and Developmental Biology programs, and the Department of Biomedical Engineering at Tufts University.

Thomas G.H. Diekwisch, DMD, PhD, PhD | Dr. Diekwisch is the Allan G. Brodie Endowed Chair for Orthodontic Research, head of the Department of Oral Biology, and director of the Brodie Laboratory for Craniofacial Genetics as well as a professor of Anatomy/Cell Biology, Bioengineering, Orthodontics, Periodontics at the University of Illinois at Chicago College of Dentistry.

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What is the Latest Thinking in Dental Stem Cell Research ...

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