Year : 2019 | Volume
: 9 | Issue : 2 | Page : 58--63
Stem cells: Redefining the future of dentistry
HN Santosh1, Aditi Bose2,
1 Department of OMRD, Sri Rajiv Gandhi College of Dental Sciences, Bengaluru, Karnataka, India
2 Department of Periodontics, Sri Rajiv Gandhi College of Dental Sciences, Bengaluru, Karnataka, India
Dr. Aditi Bose
Department of Periodontics, Sri Rajiv Gandhi College of Dental Sciences, Cholanagar, Hebbal, Bengaluru, Karnataka
Stem cells are unique cells which possess the ability to grow rapidly and have the potential to develop into specialized cell types in the body. Stem cell-based therapies in dentistry could help in new advances in treating damaged teeth, inducing bone regeneration, and even making a biological tooth a possibility. Whole tooth regeneration to replace the traditional dental implants is also in pipeline. Tissue-engineering applications using dental stem cells 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. Stem cells of dental origin have multiple applications; nevertheless, there are certain limitations as well. The oncogenic potential of these cells is still to be determined in long-term clinical studies if we are to realize the benefits, meet the challenges, and avoid the risks. This review is an attempt to highlight the pros and cons of stem cells in dentistry.
|How to cite this article:|
Santosh H N, Bose A. Stem cells: Redefining the future of dentistry.Int J Oral Health Sci 2019;9:58-63
|How to cite this URL:|
Santosh H N, Bose A. Stem cells: Redefining the future of dentistry. Int J Oral Health Sci [serial online] 2019 [cited 2022 Aug 18 ];9:58-63
Available from: https://www.ijohsjournal.org/text.asp?2019/9/2/58/270877
“When everything fails, future is the best recourse”
Man can never be God but can harness its creations to his use. Treatment with stem cell is a creative therapy that rebuilds or replaces damaged cells with tissues grown from it. Although its use in dentistry was naive, with rapid strides in stem cell research, craniofacial regeneration is a possibility not a probability. Today regeneration of craniofacial structures ranging from a tooth to temporomandibular joint (TMJ) is a reality. This has changed our perception from conservation to regeneration.
How it began………
Scientists were able to extract embryonic stem cells from mice in the 1980s, but it was not until 1998 that a team of scientists from the University of Wisconsin–Madison became the first group to isolate human embryonic stem cells and keep them alive in the laboratory. In 1998, James Thomson (University of Wisconsin–Madison) developed the first human embryonic stem cell lines. At the same time, John Gearhart at John Hopkins University isolated the primordial germ cells. From both these resources, researchers developed the pluripotent stem cell line.
What Is A Stem Cell?
Ultimately, every cell in the human body can be traced back to a fertilized egg that came into existence from the union of egg and sperm. However, the body is made up of over 200 different types of cells, not just one. All of these cell types come from a pool of stem cells in the early embryo. During early development, as well as later in life, various types of stem cells give rise to the specialized or differentiated cells that carry out the specific functions of the body, such as skin, blood, muscle, and nerve cells. This property makes stem cells appealing for scientists seeking to create medical treatments that replace lost or damaged cells.
Types of stem cells
Embryonic stem cells
Source: Harvested from 5–6-day-old embryo (blastocyst)Differentiated cell type: Any of the 200 cell types present in the human body (e.g., skin cells, liver cells, and heart cell).
Fetal stem cells
Source: Germline tissues that will make up the ovaries or testes of aborted fetusesDifferentiated cell type: All fetal tissues in the fetus before birth.
Umbilical cord stem cells
Source: Umbilical cord blood, which contains stem cells similar to those found in bone marrow of newbornsDifferentiated cell type: All blood cell types (red blood cells, white blood cells, and platelets).
Adult stem cells
Source: Resided in developed tissues, such as bone marrow, liver, skin, and the lining of gastrointestinal tractDifferentiated cell type: Develop into the same cell types.
For example, blood stem cells can develop into several blood cell types, but cannot develop into brain, kidney, or liver cells.
Stem Cell and Dental Tissue
Mesenchymal stem cells are self-renewable and can differentiate into all cell lineage that form mesenchymal and connective tissue.
Structures regenerated from mesenchymal stem cell derivatives such as nasal cartilage and TMJ from chondrocytes, craniofacial bones from osteoblasts, soft-tissue grafts from adipocyte, and dentin-pulp complex from dental pulp stem cells (DPSCs).
The above-mentioned list gives the propensity of stem cells in craniofacial regeneration areas redefined:
Tooth regenerationPeriodontal regenerationRegeneration of TMJ.
Eligibility criteria for tooth regeneration
A healthy pulp contains viable stem cells. For a pulp to be considered healthy, the tooth must have an intact blood supply and should be free of infection, deep caries, and other pathologies.
Stem cells are not concentrated within any particular area of a healthy pulp but are diffusely spread throughout the cellular zone adjacent to the nerve and blood vessels within the pulp. It is best to recover stem cells when a patient is young and healthy, and the stem cells are at their most proliferative. Stem cells can also be recovered from the permanent teeth of middle-aged individuals. The stem cells from within the pulp become less proliferative as individuals age, so it is best to recover stems cells at the earliest opportunity.
Advantages of stem cell recovery from teeth:
AccessibleAffordable and less invasiveConvenienceEase of use.
Forget dentures, dentistry eyes stem cells.
Dentin-pulp stem cells are the best choice for clinical tooth regeneration. Stem cell embedded in adult tooth socket has led to the formation of tooth crown or root. In 2009, Dr. George Huang seeded stem cells into scaffolds inserted into root canal space, and pulp was regenerated.
This proves that a bio-tooth is a reality of the future. Determining factors to extract stem cell from tooth are as follows:
Tooth with healthy pulp and caries freeDeciduous toothThird molars between 16 and 20 years.
The adult stem cells are banked. However, the economic feasibility has to be worked
Implants or whole tooth regeneration?
The ultimate goal in dentistry is to have a method to biologically replace lost teeth; in essence, a cell-based implant rather than a metal one. The minimum requirement for a biological replacement is to form the essential components required for a functional tooth, including roots, periodontal ligament (PDL), nerve, and blood supplies.
Tooth development results from sequential and reciprocal interactions between the oral epithelium and the underlying neural crest-derived mesenchyme. The generation of the entire tooth in the laboratory depends on the manipulation of the stem cells and requires a synergy of all cellular and molecular events that finally lead to the development of tooth-specific hard tissues, dentin, and enamel.
Two major cell types involved in dental hard tissue formation are the mesenchyme-originated odontoblasts, i.e. responsible for the formation of dentin and the epithelium-derived ameloblasts that form the enamel.
Mesenchymal stem cells
Mesenchymal stem cells can be isolated from different sources. First described in bone marrow, these have been extensively characterized in vitro by the expression of markers such as STRO-1, CD146, or CD44. STRO-1 is a cell surface antigen used to identify osteogenic precursors in bone marrow, CD146 a pericyte marker, and CD44 a mesenchymal stem cell marker. Mesenchymal stem cells possess a high renewal capacity and the potential to differentiate into mesodermal lineages thus forming cartilage, bone, adipose tissue, skeletal muscle, and the stroma of connective tissues.
Mesenchymal progenitors that have been assessed for tooth engineering purposes are as follows:
DPSCsStem cells from human exfoliated deciduous teethPDL stem cellsRoot apical papilla stem cellsDental follicle stem cellsEpithelial stem cells from developing molars, labial cervical loop of rodent incisorPossible application of these cells in various fields of medicine makes them a powerful tool for future research in therapeutics and tooth tissue engineering.
Dental stem cell banking
Cell preservation technology makes it possible to save valuable stem cells for future need. Stem cell banking has existed for years, and preserving stem cells by banking umbilical cord blood is already in use. With the discovery of stem cells in deciduous teeth and wisdom teeth, it provides another source of stem cell banking.
The process of stem cell banking involves three steps:
Step 1: Tooth collection.Step 2: Stem cell isolation.Step 3: Tooth cell storage: The cells are preserved in liquid nitrogen vapor at a temperature of <−150°C. This preserves the cells and maintains their potential potency.
The periodontium is a complex tissue comprised of two hard (cementum and bone) and two soft (gingiva and PDL) tissues. Once damaged, the periodontium has a limited capacity for regeneration.
Many cells are present in the PDL, including cementoblasts, osteoblasts, fibroblasts, myofibroblasts, endothelial cells, nerve cells, and epithelial cells. In addition to these, a smaller population of “progenitor cells” have been identified by in vivo cell kinetic studies. The concept that stem cells reside in the PDL tissues was first proposed by Melcher et al., in 1976, but the most compelling evidence has been provided by the in vivo and histological studies of McCulloch et al.,
The delivery of platelet-derived growth factor (PDGF) by gene transfer stimulates mitogenesis and proliferation of gingival fibroblast, PDL, and cementoblast as compared to the continuous injection of PDGF in vitro.
Adenovirus-mediated PDGF-B transfer accelerates gingival healing.Ad PDGF-B-treated wounds regenerate cementum.
Clinical application of stem cells in orofacial complex
Transplanted skeletal or dental stem cells may be used to repair craniofacial bone or repair and regenerate teeth. Transplantation of bone marrow stromal cells that contains skeletal stem cells may provide a promising alternative approach for reconstruction of craniofacial defects by circumventing many of the limitations of auto- and allo-grafting methods.
By exploiting the chondrogenic and osteogenic potential of mesenchymal cells, mandibular condyle was regeneratedin vitro within 12 weeks.
Adipocyte mesenchymal cell (AMC) along with bone morphogenetic protein 2-mediated gene therapeutics in collagen type I scaffold-induced bone formation. Human-derived AMC was combined with bone chips from the iliac crest and used to regenerate a large calvarial defect to near complete continuity.
Stem cell therapeutics could be a boon in treating certain deformities such as Marfan syndrome, osteogenesis imperfecta, and most commonly cleft lip and palate. The future in craniofacial regeneration will be to focus on the enrichment of osteoprogenitor cell within a heterogeneous population and optimization of a biocompatible scaffold.
Challenge in craniofacial tissue engineering
Challenge is to identify the relationship between bone marrow mesenchymal stem cells and the newly identified stem cells from various craniofacial tissues and how mesenchymal stress modulates craniofacial morphogenesis and regeneration needs to be further explored.
The extent to which tissue engineering should mimic or recapitulate the corresponding development events needs to be determined.
Stem Cell and Tissue Engineering
Tissue engineering deals with understanding the principles of tissue growth and applying this to produce functional replacement tissue for clinical use. It solves problem using living cells as engineering materials, which could be artificial skin, cartilage repaired with living chondrocytes.
Cells are generally implanted into an artificial structure capable of supporting three-dimensional (3D) tissue formation. These scaffolds are often critical, both ex vivo as well as in vivo, to recapitulating the in viva milieu and allowing cells to influence their own microenvironments.
New biomaterials have been engineered to have ideal properties and functional customization: injectability, synthetic manufacture, biocompatibility, nonimmunogenicity, transparency, nanoscale fibers, low concentration, and resorption rates.
Emerging trends in stem cell tissue engineering
Micro/nano-patterned biomaterials to direct stem cell differentiation
Studies revealed that not only are the dimensions of the topographical features important, but also their confirmation whether they are ridges, grooves, whorls, pits, pores, or steps and more intriguingly, even their symmetry. The advent of micro- and nano-fabrication technologies has made it possible to take apart and study independently the topographical and biochemical contribution to the cellular microenvironmental niche.
Patterning techniques, such as chemical vapor deposition, physical vapor deposition, electrochemical deposition, sofa lithography, photomicrography, electron-beam lithography, electrospinning, layer-by-layer microfluidic patterning, 3D printing, ion milling, and reactive ion etching, have been reviewed in detail by several authors. These techniques, coupled with computer-aided design tools and rapid prototyping technologies, have opened up the possibility to tailor TE scaffolds with precisely controlled geometry, texture, porosity, and rigidity.
Micro- and nano-scale patterning techniques are particularly suitable for probing stem cell interaction with their microenvironment because they allow for levels of precision compatible with the delicate regulatory control of stem cell fates.
Stem Cell Dental Implants – the Future of Implantology
The technology of dental implants has advanced rapidly in recent years to provide a solution to the aesthetic, functionality, and health issues resulting from missing teeth. However, conventional dental implants are not the perfect solution for replacing missing teeth as the healing process extends for many months, and rejection of the implant occurs in about 5% of patients. The newly evolved-stem cell dental implants could well be the future of implant dentistry.
The stem cells used are derived from tissue found at the tip of the removed tooth root, called root apical papilla. A study by Songtao Shi showed that 6 months after the stem cell implantation in the area of the removed teeth, the implants became strong enough to withstand regular use.
Since these implants are derived from stem cells from the tissue at the tooth root's tip, it significantly contributes to better tissue regeneration. These natural implants are bio-roots and can naturally form a bond with the bone. Furthermore, the bio-root does not bring with it the risk of loosening or gum disease, which is sometimes a complication with conventional implants.
Research is on to refine these techniques and develops more cost-effective stem cell technology procedures. Stem cell dental implants technology is in its infancy and is currently not an option for replacing missing teeth. Conventional techniques of implant dentistry are not likely to soon disappear as it could be many years until this new dental technology becomes commercially available.
Stem cell dental implants may be the future of implant dentistry and could have the benefits of restoring teeth in a more effective manner than traditional dental implants with the benefit of a higher success rate and greater longevity. Stem cell dental implants may be the future with the benefit of a higher success rate and greater longevity.
Stem Cell and Clinical Practice
The conjoining factor between laboratory research and clinical practice is feasibility - both economic and scientific. Stem cell banking can only store the cells. Unless active research is carried on, it cannot be used to regenerate structures. Until the time in vivo studies are proven, it will be difficult to use stem cell therapeutics. Until then – prosthetic rehabilitation would rule the roost. Besides, the progress of stem cell-based technologies depends on the regulatory pathways of the Food and Drug Administration in the USA and equivalent regulatory agencies elsewhere.
Stem cell research can potentially help treating a range of diseases. It could lead us closer to cure and rehabilitation. Stem cell pros and cons must be valued carefully. When planning to investigate a phenomenon, you cannot defend a study ethically if the cost is higher than the benefits.
The analysis needs to include human/animal discomfort, environmental issues, material costs/benefits, and economy.
There are two main issues concerning stem cell research with both pros and cons:
How the knowledge will be usedConcerns about the methods.
Pros of stem cell research
The benefits of stem cell research have such a great outcome that it outweighs the ethical issues (cost-benefit-analysis).If someone is going to have an abortion, is not it better that we use it for something useful?Adult stem cells would not be that interesting because they do not have the same properties as stem cells from a fetus.Another often mentioned advantage is that this research would give great insights into the basics of the body.
Cons of stem cell research
Critics against stem cell research, argue that there are ethical issues that do not justify the benefitsA life is a life, and that should never be compromised. A fertilized egg should be valued as a human life even if it is in its very 1st weeks. Destroying human life in the hopes of saving human life is not ethicalWe should (and will) develop more ethical methods (such as using adult stem cells) which will enable us to research ethically. We should wait to those methods as and when they are availableThe scientific value has been overstated or has flaws. For example, we do not know for sure that we can use stem cells to clone organs to be transplanted to oneself.
Benefits of stem cell research in curing diseases: Stem cell research can potentially help treating a range of medical and dental problems. It could lead us closer to cure:
The stem cell-research is an example of the, sometimes hard, cost-benefit analysis ethics scientists need to do. Stem cell pros and cons must be valued carefully. When planning to investigate a phenomenon, you cannot defend a study ethically if the cost is higher than the benefits. The analysis needs to include human/animal discomfort, environmental issues, material costs/benefits, and economy.
Stem cell therapy – Hype or hope?
While the regeneration of a lost tissue is known to mankind for several years, it is only in the recent past that research on regenerative medicine/dentistry has gained momentum and eluded the dramatic yet scientific advancements in the field of molecular biology. The growing understanding of biological concepts in the regeneration of oral/dental tissues coupled with experiments on stem cells is likely to result in a paradigm shift in the therapeutic armamentarium of dental and oral diseases culminating in an intense search for “biological solutions to biological problems.” Stem cells have been successfully isolated from a variety of human tissues, including orofacial tissues. Initial evidence from pioneering studies has documented the likely breakthrough that stem cells offer for various life-threatening diseases that have so far defeated modern medical care. The evidence gathered so far has propelled many elegant studies exploring the role of stem cells and their manifold dental applications.
Dental Pulp Stem Cell-Myriad Applications
The tooth and beyond. The application of dental stem cell expands beyond dentistry too. DPSC has shown to differentiate into neuron-like and glial-like cells by expressing both NESTIN (early marker of neural precursor cell) and glial fibrillary acid protein an antigen characteristic of glial cells. This property can be used to treat cases of Alzheimer's disease, Parkinson's disease, and dementia. Tissue-engineered condyle has served as prototype to engineer other joints such as knee and hip.
“Nothing is as dynamic as change.” Dentistry started with extension for prevention, moved to conservation and today it is regeneration. This is a result of our constant perseverance to be demi gods!
Stem cell therapy has breached the horizon and has enabled dentistry to look beyond restorations and prosthesis. However, it comes with its own limitations such as ethical issues, economic feasibility, and patient acceptance. The fact that stem cell lines have developmental plasticity can be exploited to treat even certain chronic diseases.
The challenges associated with stem cell research are isolation and identification of stem cells, conducting in vivo experiments, prevent immune rejection, and developing distinct molecular markers. Although challenges are many, to make stem cell a viable option in dentistry a systematic learning model needs to be set up; with stress on research, awareness, and continuing educational programs in the field of stem cell.
Conventional biomedical research is focused on understanding the mechanism of biological function in health and disease. However, regenerative medical research is focused on developing products capable of healing diseased tissue. This involves an understanding of the mechanism of interaction among cells, growth factors, and biomaterials.
“Science doesn't progress linearly and breakthrough is not always predicted” Only our relentless efforts and a sangfroid temperament would make - “A tooth for a tooth” possible…
In this era of evidence-based dentistry, research is essential to prove our patients that stem cell is the answer for future. “When it comes to the future, there are three kinds of people: those who let it happen, those who make it happen, and those who wonder what happened.” Its time to - “Learn the past, watch the present, and create the future.”
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||Collins JM, Russell B. Stem cell therapy for cardiac repair. J Cardiovasc Nurs 2009;24:93-7.|
|2||Huang GT. Pulp and dentin tissue engineering and regeneration: Current progress. Regen Med 2009;4:697-707.|
|3||Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970;3:393-403.|
|4||Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.|
|5||Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs)in vitro and in vivo. Proc Natl Acad Sci U S A 2000;97:13625-30.|
|6||Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al. SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 2003;100:5807-12.|
|7||Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 2004;364:149-55.|
|8||Volponi AA, Pang Y, Sharpe PT. Stem cell-based biological tooth repair and regeneration. Trends Cell Biol 2010;20:715-22.|
|9||Petrovic V, Stefanovic V. Dental tissue – New source for stem cells. ScientificWorldJournal 2009;9:1167-77.|
|10||McCulloch CA, Nemeth E, Lowenberg B, Melcher AH. Paravascular cells in endosteal spaces of alveolar bone contribute to periodontal ligament cell populations. Anat Rec 1987;219:233-42.|
|11||Melcher AH, Cheong T, Cox J, Nemeth E, Shiga A. Synthesis of cement-like tissue in vitro by cells cultured from bone: A light and electron microscopic study. J Periodont Res 1986;21:592-619.|
|12||Mao JJ, Giannobile WV, Helms JA, Hollister SJ, Krebsbach PH, Longaker MT, et al. Craniofacial tissue engineering by stem cells. J Dent Res 2006;85:966-79.|
|13||Dolatshahi-Pirouz A, Nikkhah M, Kolind K, Dokmeci MR, Khademhosseini A. Micro- and nanoengineering approaches to control stem cell-biomaterial interactions. J Funct Biomater 2011;2:88-106.|
|14||Wei F, Song T, Ding G, Xu J, Liu Y, Liu D, et al. Functional tooth restoration by allogeneic mesenchymal stem cell-based bio-root regeneration in swine. Stem Cells Dev 2013;22:1752-62. doi: 10.1089/scd.2012.0688.|
|15||Smith MH. Neuro stem cell. Stem Cell 2012;3:126-79.|