Stem cells and their application in dentistry: A review

Muraleedhara Bhat¹, Praveen Shetty², Subramanya Shetty¹, Faizan A Khan¹, Shabeeb Rahman¹, Mallikarjuna Ragher^3
1 Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka, India
² Department of Orthodontics, Srinivas Institute of Dental Sciences, Mangalore, Karnataka, India
³ Department of Prosthodontics, Yenepoya Dental College, Yenepoya University, Mangalore, Karnataka, India

Date of Web Publication

28-May-2019

Correspondence Address:
Dr. Muraleedhara Bhat
Department of Orthodontics, Yenepoya Dental College, Yenepoya University, Deralakatte, Mangalore 575013, Karnataka
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/JPBS.JPBS_288_18

Abstract

The use of the term “stem cells” dates back to the 1800s; however, the application of the same is still not completely understood. Recent advances have indicated the harvesting of postnatal stem cells from sources such as the dental pulp and fat. The pluripotent nature of these cells allows for use in various aspects of treatment and patient care such as organ and tissue transplantation, bony defects repair, distraction osteogenesis, cell therapies, gene therapy, and toxicology testing of new drugs. This article explores the various aspects involved, the current status, and future challenges of stem cell therapy in patient care and management.

Keywords: Organ transplantation, regeneration, stem cells

How to cite this article: Bhat M, Shetty P, Shetty S, Khan FA, Rahman S, Ragher M. Stem cells and their application in dentistry: A review. J Pharm Bioall Sci 2019;11, Suppl S2:82-4

How to cite this URL: Bhat M, Shetty P, Shetty S, Khan FA, Rahman S, Ragher M. Stem cells and their application in dentistry: A review. J Pharm Bioall Sci [serial online] 2019 [cited 2019 May 28];11, Suppl S2:82-4. Available from: http://www.jpbsonline.org/text.asp?2019/11/6/82/258831

Introduction

The human body has a remarkable capacity for regeneration. Cells in tissues such as blood and epithelia divide rapidly and are regenerated continually throughout life, whereas cells in most other tissues turn over more slowly and respond only to specific biological signals.^[1] For centuries, scientists have known that certain animals can regenerate missing parts of their bodies. Stem cells are unspecialized cells in the human body that are capable of becoming specialized cells, each with new specialized cell functions. The identity of the powerful cells that allow us to regenerate some tissues was first revealed when experiments with bone marrow in the 1950s established the existence of stem cells in our bodies.^[2] The first stem cells studied by researchers were derived from adult tissues, and more recently, scientific breakthroughs have enabled research on stem cells that are removed from one of the earliest human cellular formations, the blastocyst (Stem cells are basic cells of all multicellular organisms having the potency to differentiate into wide range of adult cells).^[3] A stem cell is essentially the building block of the human body. The stem cells inside an embryo eventually give rise to every cell, organ, and tissue in the fetus’s body. Unlike a regular cell, which can only replicate to create more of its own kind of cell, a stem cell is pluripotent. When it divides, it can make any one of the 220 different cells in the human body.^[4]

Dental researchers have been working with stem cells to help address both oral and systemic health problems. Through this research, postnatal stem cells have been isolated from primary teeth.^[5]

History

The first person to use the term “stem cell” was William Sedgwick in 1886 while describing the regenerative properties of the plants. A decade later, E.B. Wilson applied the term to cells in the roundworm Ascaris that retained their genetic material and appeared to regenerate. Around the same time, William Roux, using frogs, and Hans Driesch, using sea urchins, performed a set of experiments to address a set of fundamental questions.^[6] Contemporary stem cell techniques also arose from embryology work of the late 1800s and early 1900s. In 1912, Jacques Loeb successfully achieved artificial parthenogenesis, the process by which unfertilized eggs undergo chromosome duplication and rapid mitosis to establish the developing embryo.^[7] Beatrice Mintz and Karl Illmensee extended this work in the 1970s and found that when embryonic carcinoma cells are transplanted into the developing mouse embryo at the blastocyst stage, they give rise to normal mosaic mice.^[8] Around the same time, in Cambridge, biologist Robert Edwards was also experimenting with transgenic mice.^[9]

Classificationof Stem Cells

Stem cells can be classified into four broad types based on their origin:

1. stem cells from embryos;



2. stem cells from the fetus;



3. stem cells from the umbilical cord, and



4. stem cells from the adult.

Stem cells are classified according to stages of development as,

1. Pluripotent stem cells



2. Multipotent stem cells



3. Totipotent stem cells



4. Inducible pluripotent stem cells.^[10]

Uses of StemCells

Organs and tissues for transplantation: restoring vital body functions

Stem cells may hold the key to replace cells lost in many devastating diseases. Parkinson’s disease, diabetes, chronic heart disease, end-stage kidney disease, liver failure, and cancer are just a few for which stem cells have therapeutic potential. For many diseases that shorten lives, there are no effective treatments, but the goal is to find a way to replace what natural processes have taken away. Scientists in academic and industrial research are vigorously pursuing all possible avenues of research, including ways to direct the specialization of adult and embryonic stem cells to become pancreatic islet-like cells that produce insulin and can be used to control blood glucose levels.^[11]

Cell therapies

Cell therapies could be developed using human embryonic stem cells for the treatment of degenerative diseases. This can be used for Parkinson’s disease, Alzheimer’s diseases, spinal cord injury, stroke, burns, diabetes, osteoarthritis, rheumatoid arthritis, and oral diseases such as dental caries, periodontal disorders, and pulpal disorders. These can also be used for Alzheimer’s diseases, spinal cord injury, stroke, burns, diabetes, osteoarthritis, rheumatoid arthritis, and oral diseases such as dental caries, periodontal disorders, and pulpal disorders.

Gene therapy techniques

Gene therapy techniques could be improved by using genetically modified stem cells as vectors for gene insertion, for example, in cancers and birth defects. This would circumvent some of the current problems associated with gene delivery and immune reaction, which significantly impede progress in the development of effective “gene therapies.” (Gene therapy became possible through the advances of genetics and bioengineering that enabled manipulating vectors for delivery of extrachromosomal material to target cells).^[12]

Now, researchers are trying to devise more ways to use specialized cells derived from stem cells to target specific cancerous cells and directly deliver treatments that will destroy or modify them.^[13]

Toxicology testing of new drugs

Another future use of human stem cells and their derivatives includes the testing of candidate therapeutic drugs. Stem cells are likely to be used to develop specialized liver cells to evaluate drug-detoxifying capabilities and represent a new type of early warning system to prevent adverse reactions in patients (Stem cell toxicology, an emerging branch of in vitro toxicology, which offers effective and efficient alternatives to traditional toxicology assessments).^[14]

Ekizera et al.^[15] conducted a study to increase new bone formation in the sutures by transplanting bone marrow–derived mesenchymal stem cells (MSCs) into the interpremaxillary suture after rapid maxillary expansion. Histomorphometric analysis revealed that a single local injection of MSCs into the midpalatal suture increased the new bone formation in the suture by increasing the number of osteoblasts and new vessel formation, compared with controls injected with phosphate-buffered saline.

Adult stem cells have been identified in the craniofacial complex, including stem cells from craniofacial bone, dental pulp, periodontal ligament, and developing tooth bud. Utilization of adult stem cells has shown these cells to express markers consistent with differentiated tissues and cell types present within the oral cavity. Currently, studies are using adult stem cells to fabricate new tissues for replacement and regeneration of lost tissues due to trauma or disease. Additional focus is currently on the mechanism by which these stem cells produce differentiated cells expressing protein markers and having a function similar to tissues in which the stem cells were placed.^[16]

Distraction osteogenesis is becoming a method for generating new bone in the cases of alveolar bone deformities by progressively distracting bone healing surfaces, and it is essentially the bone remodeling procedure that includes mobilization of the osteoblastic/osteoclastic progenitor/stem cells. Tee and Sun^[17] reviewed the advances and limitations of recent investigations on mandibular distraction osteogenesis (MDO) assisted by MSC transplantation. Majority of studies found that MSC transplantation enhanced MDO bone regeneration and concluded that evidence from animal studies indicates that MDO may be enhanced by MSC transplantation, but many questions related to animal models, MDO protocols, and cell transplantation remain to be investigated.

Qi et al.^[18] conducted a study to observe the effects of bone marrow MSC transplantation on new bone formation in a rat mandibular osteodistraction model. Autologous bone marrow stem cells were obtained from tibiae of 40 male rats. Two weeks after cell harvest, the rats underwent right mandibular distraction and were then randomly divided into two groups (group A = 20, group B = 20). After distraction was complete, the stem cells were injected into the distracted gaps in group A, whereas the rats in group B received only physiological saline. The results showed radiodensity of the distraction zone was higher in group A than in group B at both time points. Study concluded that autologous bone marrow stem cell transplantation might be considered as a potential method to accelerate bone regeneration in the distraction gap and to enhance consolidation.

Repair of bony defects in orofacial clefts

Repair of bony defects continues to be a challenging part of many reconstructive procedures. Current techniques are plagued by some shortcomings. Although autogenous bone grafts remain the standard in the reconstruction of bony defects, there are disadvantages such as the limited amount of available bone and donor site morbidity. Artificial bone substitutes such as silicone, porous polyethylene, hydroxyapatite, and tricalcium phosphate may be used, but these may expose the patient to the risks of foreign body reactions and infections. Recent advances in cell culture techniques may provide for an elegant solution to these restrictions.^[19]

Future Challengesfor StemCell–basedGeneTherapy

Despite promising scientific results with genetically modified stem cells, some major problems remain to be overcome. Strategies that combine gene targeting with embryonic stem cell–based therapy are thus potential novel therapeutic options. Further research is essential to determine the full potential of both adult and embryonic stem cells in this exciting new field.^[20]

Conclusion

Although stem cell research and clinical utilization of stem cells are still in the initial phases, existing studies strongly suggest adult stem cell usefulness in future clinical protocols aimed at repair and regeneration during treatment of various deformities.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 

References

1.	Krebsbach PH, Robey PG. Dental and skeletal stem cells: Potential cellular therapeutics for craniofacial regeneration. J Dent Educ 2002;66:766-73.
2.	The National Academies. Understanding stem cells: An overview of science and issues from the national academies. 2017 [cited 12 March 2019]. Available from: https://bit.ly/2J5Zjoy.
3.	Kalra K, Tomar P. Stem cell: Basics, classification and applications. Am Jour of Phytomed & Clinical Therapeut 2014;2:919-30.
4.	Watson S. How stem cells works. 2017 [cited 12 March 2019]. Available from: https://science.howstuffworks.com/life/cellular-microscopic/stem-cell1.htm.
5.	Daley GQ. Missed opportunities in embryonic stem-cell research. N Engl J Med 2004;351:627-8.
6.	Maienschein J. Whose view of life? Cambridge: Harvard University Press; 2009; 58-70.
7.	Loeb J. Artificial parthenogenesis and fertilization.Tempe Arizona 85287, United States, Arizona State University, School of Life Sciences, Center for Biology and Society. Embryo Project Encyclopedias: 1913. https://embryo.asu.edu/pages/artificial-parthenogenesis-and-fertilization-1913-jacques-loeb [Last accessed 2019 Mar 10]
8.	Mintz B, Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proceedings of the National Academy of Sciences 1975;72:3585-9.
9.	Lewis R. A stem cell legacy: Leroy Stevens. The Scientist 2000;14:19.
10.	Parikh H, Kikani A, Bhatt K, Dhaka S, Shah M. Stem Cells: An Arrow In The Quiver... Does It Lead To Bull’s Eye????!!!! Journal of Ahmedabad Dental College & Hospital (JADCH) 2014;5:57.
11.	Junying YU, Thomson JA. Stem cells: Scientific progress and future research direction. J Clin Periodontol 2001;5:20-35.
12.	Gonçalves GA, Paiva RD. Gene therapy: Advances, challenges and perspectives. Einstein (Sao Paulo). 2017;15:369-75.
13.	Kirschstein R, Skirboll LR. Stem cells: Scientific progress and future research directions.Bethesda, Maryland: National Institutes of Health, Department of Health and Human Services; 2001.
14.	Liu S, Yin N, Faiola F. Prospects and frontiers of stem cell toxicology. Stem cells and development.2017;26:1528-39.
15.	Ekizera A, Yalvacb ME, Uysalc T, Sonmezd MF, Sahine F. Bone marrow mesenchymal stem cells enhance bone formation in orthodontically expanded maxillae in rats. Angle Orthod 2015;85:394-9.
16.	Guan G, Shi S, Kramer PR. Role of adult stem cells in craniofacial growth and repair. Semin Orthod 2005;11: 227-33.
17.	Tee BC, Sun Z. Mandibular distraction osteogenesis assisted by cell-based tissue engineering: A systematic review. Orthod Craniofac Res 2015;18 (suppl 1):39-49.
18.	Qi M, Hu J, Zou S, Zhou H, Han L. Mandibular distraction osteogenesis enhanced by bone marrow mesenchymal stem cells in rats. J Craniomaxillofac Surg 2006;34:283-9.
19.	Conejero JA, Lee JA, Parrett BM, Terry M, Wear-Maggitti K, Grant RT, et al. Repair of palatal bone defects using osteogenically differentiated fat-derived stem cells. Plast Reconstr Surg 2006;117:857-63.
20.	Junying YU, Thomson JA. Regenerative medicine 2006. Terese Winslow;2006;88:51.