Dental pulp stem cells (DPSCs) are

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

s present in the dental pulp, which is the soft living tissue within

teeth A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, tear ...

. They are pluripotent, as they can form

embryoid body Embryoid bodies (EBs) are three-dimensional aggregates of pluripotent stem cells. EBs are differentiation of human embryonic stem cells into embryoid bodies comprising the three embryonic germ layers. Background The pluripotent cell type ...

-like structures (EBs) ''in vitro'' and

teratoma A teratoma is a tumor made up of several different types of tissue, such as hair, muscle, teeth, or bone. Teratomata typically form in the ovary, testicle, or coccyx. Symptoms Symptoms may be minimal if the tumor is small. A testicular terato ...

-like structures that contained tissues derived from all three embryonic

germ layer A germ layer is a primary layer of cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce two or three pr ...

s when injected in nude mice. DPSCs can differentiate ''in vitro'' into tissues that have similar characteristics to

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...

and

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...

layers. DPSCs were found to be able to differentiate into

adipocytes Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...

and neural-like cells. These cells can be obtained from postnatal teeth, wisdom teeth, and

deciduous teeth Deciduous teeth or primary teeth, also informally known as baby teeth, milk teeth, or temporary teeth,Illustrated Dental Embryology, Histology, and Anatomy, Bath-Balogh and Fehrenbach, Elsevier, 2011, page 255 are the first set of teeth in the ...

, providing researchers with a non-invasive method of extracting stem cells. As a result, DPSCs have been thought of as an extremely promising source of cells used in endogenous tissue engineering. Studies have shown that the proliferation rate of DPSCs is 30% higher than in other stem cells, such as bone marrow stromal stem cells (BMSSCs). These characteristics of DPSCs are mainly due to the fact that they exhibit elevated amounts of cell cycling molecules, one being cyclin-dependent kinase 6 (CDK6), present in the dental pulp tissue. Additionally, DPSCs have displayed lower immunogenicity than MSCs. Atari et al., established a protocol for isolating and identifying the subpopulations of dental pulp pluripotent-like stem cells (DPPSC). These cells are SSEA4+, OCT3/4+, NANOG+, SOX2+, LIN28+, CD13+, CD105+, CD34-, CD45-, CD90+, CD29+, CD73+, STRO1+, and CD146-, and they show genetic stability in vitro based on genomic analysis with a newly described CGH technique.

Role in regenerative dentistry

The human mouth is vulnerable to craniofacial defects, microbial attacks, and traumatic damages. Although preclinical and clinical partial regeneration of dental tissues has shown success, the creation of an entire tooth from DPSCs is not yet possible.

Distraction osteogenesis

Distraction osteogenesis Distraction osteogenesis (DO), also called callus distraction, callotasis and osteodistraction, is a process used in orthopedic surgery, podiatric surgery, and oral and maxillofacial surgery to repair skeletal deformities and in reconstructive s ...

(DO) is a method of bone regeneration, commonly used in the surgical repair of large craniofacial defects. The area in which the defect is present is purposely broken in surgery, allowed to heal briefly, and then the bone segments are gradually separated until the area has healed satisfactorily. A study conducted in 2018 by Song et al. found that DPSCs transfected with Sirtuin-1 (SIRT1) in rabbits were more effective in promoting bone formation during DO. SIRT1-modified DPSCs accumulated significantly higher levels of calcium after osteogenic differentiation ''in vitro,'' suggesting the potential role of DPSCs in enhancing the efficiency of DO.

Calcined tooth powder

Calcine tooth powder (CTP) is obtained by burning extracted teeth, destroying the potential infection-causing material within the tooth, resulting in tooth ash Tooth ash has been shown to promote bone repair. Although recent studies have shown that calcine tooth powder- culture media (CTP-CM) does not affect proliferation, they have shown that CTP-CM has significantly increased levels of osteo/odontogenic markers in DPSCs.

Stem cells from human exfoliated deciduous teeth

Stem cells from human exfoliated deciduous teeth (SHED) are similar to DPSCs in the sense that they are both derived from the dental pulp, but SHED are derived from baby teeth, whereas DPSCs are derived from adult teeth. SHED are a population of multipotent stem cells that are easily collected, as

either shed naturally or are physically removed in order to facilitate the proper growth of

permanent teeth Permanent teeth or adult teeth are the second set of teeth formed in diphyodont mammals. In humans and old world simians, there are thirty-two permanent teeth, consisting of six maxillary and six mandibular molars, four maxillary and four mandibul ...

. These cells can differentiate into

osteocytes An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and ...

, odontoblast, and

chondrocytes Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteog ...

''in vitro''. Recent work has shown the enhanced proliferative capabilities of SHED when compared with that of dental pulp stem cells.

Potential therapeutic use of SHED

Studies have shown that under the influence of oxidative stress, SHED (OST-SHED) displayed increased levels of neuronal protection. The properties of these cells exhibited in this study suggest that OST-SHED could potentially prevent of oxidative stress-induced brain damage and could aid in the development of therapeutic tools for neurodegenerative disorders. After SHED injection into Goto-Kakizaki rats, type II diabetes mellitus (T2DM) was ameliorated, suggesting the potential for SHED in T2DM therapies. Recent studies have also shown that the administration of SHED in mice ameliorated the

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

immune imbalance in allergic rhinitis (AR), suggesting the cells' potential in future AR treatments. After introducing SHED, mice experienced reduced nasal symptoms and decreased inflammatory infiltration. SHEDs were found to inhibit the proliferation of T lymphocytes, increase levels of an anti-inflammatory cytokine, IL-10, and decrease the levels of a pro-inflammatory cytokine, IL-4. Additionally, SHED can potentially treat liver

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...

. In a study conducted by Yokoyama et al. (2019), SHED were differentiated into

hepatic stellate cells The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is ...

. They found that when hepatic cells derived from SHED were transplanted into the liver of rats, liver fibrosis was terminated, allowing for the healing of the liver structure.

History

*In 2000, a population of odontogenic progenitor cells with high self-renewal and proliferative capacity was identified in the dental pulp of humans permanent third molars. * 2005 NIH announces discovery of DPSCs by Dr. Irina Kerkis * 2006 IDPSC Kerkis reported discovery of Immature Dental Pulp Stem Cells (IDPSC), a pluripotent sub-population of DPSC using dental pulp organ culture. * 2007 DPSC 1st animal studies begin for bone regeneration. * 2007 DPSC 1st animal studies begin for dental end uses. * 2008 DPSC 1st animal studies begin for heart therapies. * 2008 IDPSC 1st animal study began for muscular dystrophy therapies. * 2008 DPSC 1st animal studies begin for regenerating brain tissue. * 2008 DPSC 1st advanced animal study for bone grafting announced. Reconstruction of large size cranial bone defects in rats. * 2010 IDPSC 1st human trial for

cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...

replacement