Overview of regenerative dentistry and stem cells for dental applications

Teeth are the most natural, noninvasive source of stem cells. Dental stem cells, which are easy, convenient, and affordable to collect, hold promise for a range of very potential therapeutic applications. We have reviewed the ever-growing literature on dental stem cells archived in Medline using the following key words: Regenerative dentistry, dental stem cells, dental stem cells banking, and stem cells from human exfoliated deciduous teeth. Relevant articles covering topics related to dental stem cells were shortlisted and the facts are compiled. The objective of this review article is to discuss the history of stem cells, different stem cells relevant for dentistry, their isolation approaches, collection, and preservation of dental stem cells along with the current status of dental and medical applications.

Regenerative capacity of the dental pulp is well-known and has been recently attributed to function of dental stem cells. Dental stem cells offer a very promising therapeutic approach to restore structural defects and this concept is extensively explored by several researchers, which is evident by the rapidly growing literature in this field. For this review article a literature research covering topics related to dental stem cells was made and the facts are compiled.

Human dental stem cells that have been isolated and characterized are:

• DPSCs.(Dental pulp stem cells)
• SHED.(Stem cells from human exfoliated deciduous teeth)
• Stem cells from apical papilla (SCAP).
• Periodontal ligament stem cells (PDLSCs).

Dental pulp stem cells

DPSCs are mesenchymal type of stem cells inside dental pulp. DPSCs have osteogenic and chondrogenic potential in vitro and can differentiate into dentin, in vivo and also differentiate into dentin-pulp-like complex. Recently, immature dental pulp stem cells were identified which are a pluripotent sub-population of DPSC generated using dental pulp organ culture.

DPSCs are putative candidate for dental tissue engineering due to:

• Easy surgical access to the collection site and very low morbidity after extraction of the dental pulp.
• DPSCs can generate much more typical dentin tissues within a short period than nondental stem cells.
• Can be safely cryopreserved and recombined with many scaffolds.
• Possess immuno-privilege and anti-inflammatory abilities favorable for the allotransplantation experiments.

Stem cells from human exfoliated deciduous teeth

Dr. Songtao Shi discovered SHED in 2003. It was confirmed that SHED were able to differentiate into a variety of cell types to a greater extent than DPSCs, including osteoblast-like, odontoblast-like cells, adipocytes, and neural cells. Abbas investigated the possible neural crest origin of SHED. The main task of these cells seems to be the formation of mineralized tissue, which can be used to enhance orofacial bone regeneration.

Types of stem cells present in human exfoliated deciduous teeth are

• Adipocytes: Can be used to treat various spine and orthopedic conditions, Crohn’s disease, cardiovascular diseases and may also be useful in plastic surgery.
• Chondrocytes and osteoblasts: Have been used to grow intact teeth in animals.
• Mesenchymal stem cells (MSCs): Have successfully been used to repair spinal cord injury and to restore feeling and movement in paralyzed human patients. They can also be used to treat neuronal degenerative disorders such as Parkinson’s disease, cerebral palsy, Alzheimer’s disease, and other such disorders. MSCs have better curative potential than other type of adult stem cells.

Advantages of banking SHED cells include: It’s a simple painless technique to isolate them and being an autologous transplant they don’t possess any risk of immune reaction or tissue rejection and hence immunosuppressive therapy is not required. SHED may also be useful for close relatives of the donor such as grandparents, parents and siblings. Apart from these, SHED banking is more economical when compared to cord blood and may be complementary to cord cell banking. The most important of all these cells are not subjected to same ethical concerns as embryonic stem cells.

POTENTIAL APPLICATIONS IN DENTISTRY
Most research is directed toward regeneration of damaged dentin, pulp, resorbed root, periodontal regeneration and repair perforations. Whole tooth regeneration to replace the traditional dental implants is also in pipeline. Tissue-engineering applications using dental stem cells that may promote more rapid healing of oral wounds and ulcers as well as the use of gene-transfer methods to manipulate salivary proteins and oral microbial colonization patterns are promising and possible.[31]

The use of stem cells in osseous regeneration

Adult MSCs recently identified in the gingival connective tissues (gingival mesenchymal stem cells [GMSCs]) have osteogenic potential and are capable of bone regeneration in mandibular defects. GMSCs also suppress the inflammatory response by inhibiting lymphocyte proliferation and inflammatory cytokines and by promoting the recruitment of regulatory T-cells and anti-inflammatory cytokines. Thus, GMSCs potentially promote the “right” environment for osseous regeneration and is currently being therapeutically explored.

Nondental stem cells for dental application

Researchers of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell Biology and Regenerative Medicine, reported a possible method for growing teeth from stem cells obtained in urine. In this study, pluripotent stem cells derived from human urine were induced to generate tooth-like structures in a group of mice with a success rates of up to 30%. The generated teeth had physical properties similar to that of normal human teeth except hardness (about one-third less in hardness of human teeth). The reported advantages to such an approach were being noninvasive technique, low cost, and use of somatic cells (instead of embryonic) that are wasted anyways. Interestingly urine-derived stem cells do not form tumors when transplanted in the body unlike other stem cells; more over autologous sourcing of these cells reduces the likelihood of rejection.

PROSPECTS OF DENTAL STEM CELLS IN MEDICINE

Dental stem cells have the potential to be utilized for medical applications like heart therapies, regenerating brain tissue, for muscular dystrophy therapies and for bone regeneration. SHED can be used to generate cartilage as well as adipose tissue. In 2008 first advanced animal study for bone grafting was announced resulting in reconstruction of large size cranial bone defects in rats with human DPSCs.

FUTURE PROSPECTIVES

Researchers have observed promising results in several preclinical animal studies and numerous clinical trials are now on-going globally to further validate these findings. The Obama administration has made stem cell research one of the pillars of his health program. The U.S. Army is investing over $250 million in stem cell research to treat injured soldiers in a project called Armed Forces Institute for Regenerative Medicine. It is likely that the next stem cell advance is the availability of regenerative dental kits, which will enable the dentists the ability to deliver stem cell therapies locally as part of routine dental practice. An innovative method that holds promising future is to generate induced stem cells from harvested human dental stem cells. This approach reprograms dental stem cells into an embryonic state, thus expanding their potential to differentiate into a much wider range of tissue types. Researchers have so far succeeded in making specific dental tissues or tooth like structures although in animal studies but future advances in dental stem cell research will be the regeneration of functional tooth in humans.

SOURCE – Journal of Natural Science and Biology