Stem Cells in Prosthodontics

Abstract

The ultimate goal for tissue engineering and regenerative medicine is to develop therapies to restore lost, damaged, or aging tissues using engineered or regenerated products derived from either donor or autologous cells. Cell-based therapies are the most common approaches in regenerative medicine. Challenges in applying this approach clinically are to acquire the appropriate source of cells, to identify methodologies to induce cell proliferation and differentiation, to maintain cell survival, and to remove unwanted cells. This review of article presents the current scenario of treatment modalities which are available or under clinical trials offered by tissue engineering in the field of prosthodontics.

Key Words:Stems cells, Tissue Engineering, REgenerative medicine.

INTRODUCTION

Recent exciting new discoveries place dentists at the forefront of helping their patients benefit from potentially life-saving therapies derived from a patient’s own stem cells obtained from deciduous teeth and permanent teeth.The great hope is that suitable stem cells, produced in large quantities through cell culture methods and injected into failing tissues and organs, will produce fresh, replacement cells to take over from lost or damaged ones. It is now known that adult stem cells taken from one area of the body can be transplanted into another area and grown into a completely different type of tissue. This ability to grow and regenerate tissues is the focus of the emerging field of personalized medicine which uses a patient’s own stem cells for biologically compatible therapies and individually tailored treatments.The dental professional will play an important role in both the recovery and the use of these stem cells in both Dental and Medical regenerative therapies.

STEM CELLS1

Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. Stem cells are unspecialized cells that develop into the specialized cells that make up the different types of tissue in the human body.

Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues.

TYPES OF STEM CELLS & THEIR CHARACTERISTICS

There are two major types of stem cells, Embryonic and Adult stem cells. One Embryonic stem cell has the potential to differentiate into all 220 types of specialized cells that make up the human body.Adult stem cells are responsible for the regeneration and replacement of tissue damaged by disease or injury.

EMBRYONIC STEM CELLS

Embryonic stem cells are the result of the fertilization of an egg by a sperm. Cells produced by the first few divisions of the fertilized egg are totipotent. At about the fifth day this ball of cells becomes a blastocyst, an early stage embryo that is made up of 50-150 cells. Pluripotent stem cells are those embryonic stem cells that are harvested after the fifth day from the inner mass of this blastocyst. These pluripotent stem cells go on to differentiate into any of the three types of cells that derive the germ layers: ectoderm, endodem and mesoderm. These stem cells are then called multipotentor adult stem cells and form around day 14.

ADULT STEM CELLS

Adult stem cells are usually designated according to their source and their potential. Adult stem cells are multipotent because their potential is normally limited to one or more lineages of specialized cells. However, a special multipotent stem cell that can be found in bone marrow and dental pulp is called the mesenchymalstem cell and can produce different cell types: bone, cartilage, fat, muscle, and connective tissues

STEM CELLS IMPLICATION IN PROSTHODONTICS

In dentistry, tissue engineering is also considered to be a new frontier in the regeneration of missing oral tissues/organs.2 For example, various degrees of alveolar bone resorption occur after tooth loss/extraction because of periodontal disease, severe caries, root fractures or accidental trauma. In addition, the bone resorption in the residual ridge, particularly in the mandible, continues throughout life in many edentulous patients3.The severe bone resorption in edentulous areas makes it difficult to restore the missing teeth with dental implants or denture treatment.Therefore, stem cell and tissue engineering therapies are expected to provide a novel capability to regenerate large defects in periodontal tissues and alveolar bone, and to ultimately replace the lost tooth itself. The tissues and organs targeted for such regenerative medicine strategies in dentistry include the salivary gland, tongue and craniofacial skeletal muscles , as well as the condylar cartilage of the temporomandibular joint.4,5

BIOENGINEERED TOOTH

In the early 1990s, Langer and Vacanti conceived a new concept, tissue engineering to produce biological tissues or whole organs by seeding a prefabricated, biodegradable scaffold with specialized cells capable of generating the tissue or organ of interest.6

Several groups have reported techniques for the production of biological teeth based on embryonic tooth cell–tissue or cell–cell recombination in the kidney capsule.7In 2002, Jung et al. reported the use of constructs from intact dental epithelium in combination with isolated and reaggregated dental mesenchymal cells from mouse teeth at the late bud stage.

It has beenpreviously reported that bioengineered tooth germ can successfully develop a bioengineered tooth by subrenal capsuletransplantation and can restore a mature tooth, including periodontaltissue and alveolar bone.8 Because a three-dimensional in vitroorgan culture has not yet been developed, a strategyinvolving a bioengineered tooth unit, which has the necessary tissuesto restore tooth functions, to investigation and advance the futurepotential of bioengineered tooth replacement is employed. Thebioengineered molar tooth germ was developed to a stage equivalentto the early bell stage of natural tooth germ for 5–7 days in an in vitro organ culture. Although it has been stated that multiple bioengineered teeth have been formed from a bioengineered tooth germ reconstituted by organ germ method.

The bioengineered tooth germ gradually accumulated hard tissue, root extension, and an increased alveolar bone volume, depending on transplantation periods, and could successfully generate a tooth unit with the correct structure of a whole molar, and the proper formation of periodontal tissue and surrounding alveolar bone. However, the shape (x vs.y axis) of the bioengineered tooth unit was flattened by the pressure of the outer membrane of the sub renal capsule. The length of the tooth also showed continuous root elongation depending on the transplantation periods without occlusional mechanical stress.To generate the shape- and length-controlled bioengineered tooth unit so that a suitable size was obtained for intraoral transplantation, the tooth germ was inserted into a ring-shaped size-control device and then transplanted into a subrenal capsule.The device thus successfully generated a size-controlled bioengineered tooth so that it was similar to a natural tooth. This device could avoid the pressure by the subrenal capsule membrane, and reserve the three-dimensional space for developing a bioengineered tooth germ normally.

These findings resulted in a new concept in tooth regeneration therapy: the transplantation of a bioengineered tooth has great potential for not only whole tooth regenerative therapy but also as a treatment in clinical cases where tooth loss is accompanied by a serious alveolar bone defect.One of the major hurdles in the clinical application of tooth regeneration technology is the identification of an appropriate autologous stem cell source in humans. In this regard, iPS cells may be an appropriate cell source because they can be differentiated to dental epithelial and mesenchymal cells and can be prepared from the patients’ own somatic cells.9

CHAIR-SIDE CELLULAR GRAFTING APPROACH17

The other approach to stem-cell-based bone regeneration relies on the direct use of a patient-derived fresh cellular graft prepared at the chair-side or a commercially prepared allograft bone matrix that contains native MSCs (prepared from cadavers).These procedures are relatively convenient for clinicians because they do not require laboratory support or extensive training.10

In 2006, Smiler and Soltan11first reported a technique for chair-side cellular graft preparation using fresh aspirated bone marrow from the ilium that was mixed with a resorbable matrix, and they also showed bone marrow aspirate that was transplanted with biocompatible scaffolds or allograft bone blocks could successfully regenerate bone.

Thereafter, cellular grafting approaches using the mononuclear fraction obtained from processed fresh marrow have been well documented. This method has been developed as a system called ‘‘Bone Marrow Aspirate Concentrate (BMAC)’’. The mononuclear fraction contains two principal lineages of stem cells: one responsible for hematopoiesis and another regarded as an MSC population.MSCs prepared by the chair-side method and combined with BBM (bovine bone mineral,Bio-Oss) particles have been shown to form lamellar bone and provide a reliable base for dental implants.

An interesting aspect of the chair-side method is that no clinical or histologic inflammatory response was observed after the operation.The cells in freshly processed grafts are not completely homogeneous and may contain several cell types, such as MSCs, osteogenic cells, hematopoietic cells, angiogenic cells and stromal cells. Therefore, the freshly prepared cellular grafting material may behave somewhat similarly to a primitive bone niche to provide easier acceptance by the host environment without an unfavorable local inflammatory reaction.

MANDIBLE CONDYLE REGENERATION12

Damage to the temporomandibular joint disc or condyle (condylar osteochondral defect) arising from trauma or arthritis can result in lifelong pain and disturbed masticatory function for patients. Tissue regeneration strategy on these defects can hold promise to affect the quality of life of these patients.

In a goat model, the combination of cartilage tissue engineering using cartilage-derived progenitor cells carried in a hydrogel and distraction osteogenesis was successfully used to reconstruct condylar osteochondral defects.12

Additionally, a human-shaped mandibular condyle was successfully engineered from chondrogenically and osteogenically induced rat BMSCs encapsulated in a biocompatible polymer.13MSCs were isolated from femoral and tibial bone marrows of adult rats and exposed separately to either chondrogenic or osteogenic supplemented culture medium.MSC derived chondrogenic and osteogenic cells were encapsulated in PEGDA hydrogel into a negative mold of an adult human cadaver mandibular condyle in two stratified and yet integrated layers.Thephotopolymerizedosteochondral construct was implanted into the dorsum of immunodeficient mice for up to 12 wks.

De novoformation of a structure having the same shape and dimensions as the cadaver human mandibular condyle was observed after 4 wks of in vivoimplantation.The tissue-engineered mandibular joint condyles retained the macroscopic shape and dimensions of the cadaver mandibular condyle.13

STEM CELLS FOR BONE REGENERATION

A modern strategy in Regenerative Medicine is the approach to combine living cells and scaffold material to establish a biological alternative for the diseased organ or tissue that can restore the functions.Some degradable polymers, ceramics, or a combination of both can provide desirable mechanical and osteoconductive properties as basic scaffold material for bone replacement.Different factors should be considered for the use of such a biomaterial scaffold. It should imitate the three dimensional environment of the extracellular matrix, it should provide stability until replaced by regrown bone tissue and serve as an extended surface area for migration, adhesion, and differentiation of cells to encourage the growth of new tissue.The proliferating cells cover the scaffold and can grow into three dimensional tissue within. They are also an important factor for forming new tissue through extracellular matrix synthesis (Bonassar & Vacanti, 1998).

Due to the development of new blood vessels towards, and to some extent onto, the new tissue, the scaffold begins to degenerate from the outside and is reconstituted by new natural bone tissue. As tissue related cell types cannot always be obtained in an adequate number or quality, SCs are a useful alternative for tissue regeneration.

There are defects of the alveolar bone which occur as a result of trauma, inflammation,resective surgical intervention such as tumor resection, bone loss after periodontal disease or athrophia after tooth loss or agenesis. In the posterior maxilla the phenomenon of pneumatization of the sinus maxillaris increases after tooth loss, which results in a vertical compromized bone level.

Thus, bone reconstruction before or simultaneously to implant placement is often necessary. To do so guided, bone regeneration with autologous material such as bone graft material or other autologous or artificial grafting procedures are methods of choice. Nevertheless, there exist many unsolved problems such as e.g. higher morbidity in conjunction with the second wound of the donor site.

Therefore the use of stem cells (SCs) as source material for bone regeneration could represent an interesting approach for dental implantology1

CONCLUSION

The advent of stem cells in repair and regeneration of the oral and dental structures have paved the way of prosthodontics from the conventional xenodontic treatment protocol to a more acceptable and natural biodontic treatment measures.Current active research areas of stem-cell-based therapy in dentistry are focused on tissue engineering and chair-side cellular grafting approaches that may result in more predictable regenerative outcomes in the future.More intensive basic and translational research is necessary, and clinical randomized controlled trials with long durations should be performed to advance the field using scientific evidence that can ultimately offer long-term benefits to patients.

REFERENCES