An overview of stem cells in dentistry

Introduction

Stem cells (SC) are undifferentiated/ immature cells that can differentiate into more specialized, tissueorgan-specific cells that have good system repairing capabilities.¹ The SC are thus referred to as “progenitor/ precursor/ clonogenic cells” that are capable of both selfrenewal and multi-lineage differentiation.² There are two types of stem cells, mainly adult stem cells (ASC) and embryonic stem cells (ESC). Teeth are the most noninvasive source of stem cells. Dental stem cells (DSC) are easy, convenient, affordable, and hold promise for a range of therapeutic applications. A variety of stem cells originate from dentistry such as periodontal ligament stem cells (PDLSC), dental pulp stem cells (DPSC), stem cells from human exfoliated deciduous teeth, stem cells from apical papilla (SCAP), and dental follicle progenitor stem cells (DFPCs).³

History:

The term “stem cell” appeared for the first time in the work of German biologist Haeckel in 1868.⁴ The term stem cell was first coined by Wilson.⁵ Russian histologist, Alexander Maksimov postulated the existence of hematopoietic stem cells at the congress of the hematologic society Berlin in 1908.⁶ G.L Feldman in 1932 showed evidence of regeneration of dental pulp under optimal conditions.⁷ Gronthos et al. in the year 2000 identified, and isolated odontogenic progenitor cells in adult dental pulp, which is a breakthrough in dental history.⁸

How stem cells work:

They have the capacity of performing three important functions

• Plasticity: Under special conditions, adult stem cells can generate a whole spectrum of cell types of other tissues even crossing germ layers which is referred to as transdifferentiation.

• Homing: These cells migrate to the site of tissue damage.

• Engraftment: To unite with other tissues.⁹

Identification of DSC:

The DSC are identified by methods such as:

1. Fluorescent antibody cell sorting: Stem cells can be identified and isolated from a mixed cell population by staining cells with specific antibody markers.

2. Immunohistochemical staining.

3. Immunomagnetic bead selection

4. Physiological and histological criteria.¹⁰

Stem cell culturing techniques:

“Cell culture” is a technique of growing cells in the laboratory (in vitro). The respective cells have to be settled on a natural or artificial extracellular matrix (ECM) and this material is called the scaffold. Human ESC is isolated by transferring inner cell mass with the help of a pipette to a plastic laboratory culture dish containing a culture medium. Recently, a device that cultivates ESC without the mouse feeder cells, was reported, which avoids the risk of viruses or other macromolecules being transmitted to humans from mouse cells. The cells of the inner cell mass proliferate and crowd the culture dish in a few days. When this occurs, they are removed gently and plated into several fresh culture dishes. The process of re-plating the cells is repeated many times and for many months and is called sub-culturing. Various methods for culturing SC in Petri dishes, spinner bottles, rotating bioreactors, hollow fiber modules, perfusion containers, and tissue carriers.¹¹

Potential implications of stem cells in dentistry:

Table 1 shows the various characteristics of dental stem cells.

Dental pulp stem cells (DPSCs)

These stem cells are obtained from the pulp of third molar teeth. The main characteristic of DPSCs is that they may differentiate between osteogenic, cementogenic, chondrogenic, and myogenic lineages. These stem cells are easily accessible and found across all ages. Furthermore, cryopreservation does not affect their properties.¹² DPSCs undergo enzymatic digestion and their expression markers are STRO-1, CD146, CD105, CD73, CD90, CD59, CD44, CD29, and CD13.¹³ The DPSCs are characterized by mineral nodules and polarized cellular bodies that result in odontoblastic differentiation.¹⁴ 

Stem cells from apical papilla (SCAP)

These stem cells are loose connective tissue located at the apex of permanent teeth pulp. Apical papilla contains a richer source of mesenchymal SC compared to the dental pulp. They can differentiate into dentin-like structures in vivo, underscoring their inherent odontogenic potential. They are also assumed to come from the collection of SC odontoblasts which contribute to cementum formation.¹⁵ These stem cells express different markers which include STRO-1, CD146, CD105, CD90, CD73, and CD24. The neural cell markers neurofilament M, neuron-specific enolase (NSE), tubulin, glial fibrillary acidic protein (GFAP), glutamic acid decarboxylase (GAD), nestin, NeuN, uIII, CNPase, survivin (anti-apoptotic protein), human telomerase reverse transcriptase (HTERT), osteogenic/dentinogenic markers, dentin sialoprotein (DSP), FGFR3 are rooted to SCAP. This confers a high potential for adipogenic, osteogenic, dentinogenic, and neurogenic differentiation.¹⁶

Stem cells from human exfoliated deciduous teeth (SHED)

These stem cells can be of extraordinary origin for Stem cells (SC) to isolate. Various cells, such as myocytes, chondrocytes, nerve cells, adipocytes, and osteoblasts can be distinguished from these stem cells. The potential of these isolated cells includes induction of dentin and bone formation and in vitro differentiation into nondental mesenchymal cell derivatives. Their form, shape, and structure are comparable to DPSCs. They show the formation of tissues such as ectopic in vivo, but dentinpulp nexus regeneration remains a task.¹⁷

Periodontal ligament stem cells (PDLSC)

Periodontal ligament stem cells have been considered an ideal candidate for periodontal regeneration since they can be easily recovered by non-invasive procedures after simple tooth extraction. In addition, they can be cultured. They have soft connective tissue that surrounds teeth and alveolar bone. The periodontal ligament is an important supporter in maintaining the tooth, maintaining periodontal tissue homeostasis, and ensuring its regeneration.¹⁸ These stem cells express mesenchymal SC markers (CD146 and STRO-1) like DPSCs but scleraxis (tendon-specific transcriptional factor) expression occurs at higher levels compared to DPSCs. The expression of bone sialoprotein, ALP, type I transforming growth factor-E receptor, and osteocalcin which relate to bone/cementum formation have also been reported to be secreted by PDLSCs.¹⁹ Also, immunomodulatory properties i.e. low response T-cell inactivation following antigen encounter for a limited time induced by prostaglandin E2 (PGE2) is exhibited by PDLSc²⁰.

Tooth germ progenitor cells (TGPCs)

These cells are multipotent SC populations, which are isolated by mesenchymal tissue of third molars (identified due to their stable spindle-shaped morphology in the bell stage).²¹ In vitro studies showed evidence of vascularization induced by these cells. Also, TGPCs may form into hepatocytes associated with morphological changes from fibroblast-like cells to more epithelial like cells. They express the typical mesenchymal SC markers (STRO-1, CD166, CD106, CD105, CD90, CD73, CD44, CD29) and multipotency-related transcription factors (Nanog, C- myc, Sox2, Oct4, and Klf4 ). Similar to the other DSCs, TGPCs have osteogenic or odontogenic, neurogenic differentiation capacity, chondrogenic, and adipogenic potential.²²

Dental follicle progenitor cells (DFPCs)

Dental follicle progenitor cells are present in teeth that grow and play an important role in the formation of cementum, periodontal ligaments, and alveolar bone. They are obtained from the 3^rd molar follicle and it is documented that they can remain in cell culture until sections. DFSCs are differentiated whilst they can form cementum in vivo and osteoblasts, adipocytes, and nerve-like cells in vitro. They express notch-1, nestin, CD29, CD44, CD105.²³

Summary

The advancement of science has transformed our lives in ways that would have been an unpredictable halfcentury ago. Stem cells have multiple applications in medicine/dentistry in achieving complete restoration of the integrity (structural and functional) of the native tissue or organ. In dentistry, they are derivatives of the dental/apical papilla, PDL, and even carious deciduous teeth. Dental stem cells (DSC) have unique features such as a high proliferative rate, vast differentiation potential, and poor immunogenic effects making them appropriate for regenerative therapy. Given the ability of DSCs to form chondrocytes, osteocytes, and adipocytes in vitro, cultures of non-dental tissue (heart, skeletal muscle, spinal cord, brain, blood vessels, and cornea) may aid in a vast range of tissue repair/recovery. Complementary studies are recommended to identify the novel aspects of the use of DSCs in regenerative medicine.

Conflicts of interest

There were no conflicts of interest related to this study.