STEM CELL THERAPY - FUTURE OF MODERN DENTISTRY

One of interesting topic in dental treatment is stem cell therapy

Because once the teeth is lost it cannot be regenerate teeth helps variety of way in day to daily life such as grinding the teeth, speech ie., phonetic but once teeth is lost all these are lost and not only helpful for these it also a major part of cosmetic all of them unknowingly notice our teeth first 

Degenerative treatment such as root canal, filling, ect., these are grind our natural teeth and eventually our natural teeth is lost

All these problem stem cell therapy will be answer for this it is involved by regenerating our natural teeth such as enamel, dentin, pulp, cementum ect., 

Let in this article we see about the overview of stem cell therapy 

TOOTH ANATOMY

• Enamel: The hardest, white external part of the tooth.it consists of 96% of mineral which is hydroxyapatide crystall. 

• Dentin: A layer hidden the lacquer. It is a hard tissue that contains minute cylinders. At the point when the enamel is harmed, warmth or cold can enter the tooth through these ways and cause sensitivity or agony.

• Pulp: The milder, living inward structure of teeth. Veins and nerves go through the pulp of the teeth. 

• Cementum: A layer of connective tissue that ties the underlying foundations of the teeth solidly to the gums and jawbone. 

• Periodontal ligament : Tissue that helps hold the teeth firmly against the jaw

Photo credit: www.britannica.com (accessed:2/06/2020)

DEVELOPMENT OF TEETH

• Bud Stage

This 1st stage happens at the eighth week in utero. At this point, cells referred to as dental epithelial tissue bud from a thick band of cells known as the dental lamina, that forms within the higher and lower jaws. These cells can eventually evolve to make the tooth germ, that is created of all the soft tissues necessary to grow a tooth.

• Cap Stage

During this stage, cells begin to form the surface layer of the tooth, forming a cap that sits on the rest of the tooth bud. this cover is named the enamel organ as a result of it'll later kind the cells that turn out enamel. the remainder of the tooth bud, referred to as the dental papilla, can create the 2 interior layers of the tooth: 

• the dentin 
• the pulp.

Another sac of cells, known as the dental follicle, surrounds each the enamel organ and also the dental papilla. This sac contains blood vessels and nerves. By the cap stage, 3 totally different structures structure the tooth germ:

•  the enamel organ,

• the dental papilla and also the 

• dental follicle .

• Bell Stage

At now, the enamel organ grows into a bell, and 2 events occur. First, cells of the enamel organ differentiate, that means they modify functions. reckoning on their new operate, they'll comprise one among four cell groups:

• Inner enamel epithelium

Outer enamel epithelium

• Stratum intermedium
• Stellate reticulum

Together, these cell groups work to develop the enamel layer of the tooth. throughout the second event during this stage, the enamel epithelial tissue folds into the longer term form of the tooth crown, and also the dental lamina starts to interrupt down.

• Crown and Root Formation

The outer 2 layers of your teeth, enamel and dentin, kind throughout the crown stage. formative cell cells are answerable for making enamel, whereas odontoblast cells produce dentin. These cells return from the enamel epithelial tissue and also the dental papilla.

The complex body part, made from root dentin and root canals (where dental pulp lives), forms from a mixture of 3 structures: the dental papilla, the dental follicle and another necessary cluster of cells referred to as Hertwig's epithelial root sheath.

• Eruption Stage

Once the crown of the tooth has shaped and also the root has begun to develop, the tooth moves vertically toward the oral cavity thus it will erupt into the proper position. a number of the jawbone higher than the tooth can reabsorb and alternative connective tissues will break right down to facilitate the tooth move. reckoning on the sort and position of the tooth, every can erupt at totally different ages. Primary teeth can erupt initial, beginning around 6 months of age, according to the american Dental Association.

The permanent teeth can develop within the same manner because the primary teeth, starting at twenty weeks in utero and continued ten months when birth. The third molars, or wisdom teeth, aren't fully shaped till a personal is around five years. 

Photo credit: https://onlinelibrary.wiley.com https://doi.org/10.1111/adj.12102 (accessed: 02/06/2020)

MILESTONE OF STEM CELL IN DENTISTRY

STEM CELL IN TEETH

There are 4 different type of stem cell of teeth includes

• Periodontal stem cell

• Dental pulp stem cell

• Stem cell from apical papilla 

• Dental follicle stem cell

Photo credit: www.pocketdentistry.com(accessed:2/06/2020)

PERIODONTAL STEM CELL

periodontal regeneration is basically a re-enhancement of the event method together with morphogenesis, cyto diferentiation, extracellular  matrix production and mineralization, such processes support the construct that some mesenchymal stem cells stay at intervals the periodontal ligament and are accountable for tissue equilibrium.

These mesenchymal stem cells function a supply of renewable ancestor cells generating cementoblasts, osteoblasts, and fibroblasts throughout adult life. 

The periodontal ligament somatic cell cultures exhibit roughly 30% higher rates of proliferation compared to the expansion of cultivated bone marrow stromal stem cells. 

The reputed vegetative cell marker, STRO-1, accustomed isolate and purify bone marrow stromal stem cells, is additionally expressed by human periodontal ligament stem cells and dental pulp stem cells.

These studies showed that PDLSCs gift with self-renewal and multilineage differentiation capabilities, expression of mesenchymal somatic cell surface markers akin to CD44, CD73, CD 90, CD105, CD106 (VCAM-1), CD146 (MUC-18), and Stro-1, and lack of expression of hemopoietic markers similar to CD31, CD34, and CD45

it's additionally been incontestable  that pdlSCs are ready to generate PDL attachment in vivo by forming Sharpey’s fiber-like collagen bundles that are connected to cementum-like structure.

These distinctive options of PDLSCs create them a promising cell supply for cell-based regenerative odontology therapy. Hence, many studies have evaluated the potential of those cells for regeneration of periodontal defects

periodontal defect was treated with a mixture of alloplasts (hydroxyapatite and tricalcium phosphate) and cultured autologous PDLSCs; results showed recently shaped bone, cementum, and odontology ligament within the treated defect, supporting the feasibleness of odontology regeneration therapies

DENTAL PULP STEM CELL (DPSC)

DPSCs are typically found in extremely vascularized regions of the pulp and might be collected from the pulp tissue of clinically extracted human teeth of each young and aged people by numerous isolation strategies

DPSCs categorical mesenchymal vegetative cell surface markers equivalent to CD10, CD13, CD29, CD44, CD59, CD73, CD90 and CD105, and don't express CD14, CD34, CD45, HLA-DR 

It has been shown that DPSCs may be differentiated by modulation with growth factors, transcriptional factors, extracellular  matrix proteins and receptor molecules into totally different cell sorts include odontoblast, osteoblast, chondrocyte, cardiomyocytes, somatic cell cells, adipocyte, tissue layer vegetative cell, melanoma cell and endocrine secreting Beta cells

DPSCs are largely derived from cranial neural crest cells as a result of they expressed GFAP, HNK-1, Nestin, P75 and S-100 that are neural crest- somatic cell markers
DPSCs have high potential to function an honest resource for treatment in neurodegenerative diseases

• Identification of dental pulp stem cells by
• Fluorescent antibody cell sorting
• Immunomagnetic bead selection.
• Immunohistochemical staining.
• Physiological and histological criteria, which includes phenotype, proliferation, chemotaxis, mineralizing interest and differentiation.

• Various conventional methods to isolate stem cells from dental pulp are listed below are
• Size-sieved isolation
• Stem cell colony cultivation
• Magnetic activated cell sorting (MACS) 
• Fluorescence activated cell sorting (FACS)

Photo credit: https://link.springer.com/article/10.1007/s40496-014-0012-0 

STEM CELL FROM HUMAN EXFOLIATED DECIDUOUS TEETH

Multipotent somatic cell population are often isolated from the remnant pulp of human exfoliated deciduous teeth. 

SHED have higher proliferation rates, type a sphere-like clusters and differentiate into osteoblasts however they're unable to regenerate complete dentin and pulp-like complexes in vivo

Similar to DPSCs, stem cells from exfoliated deciduous teeth (SHED) have the capability to differentiate into osteogenic, adipogenic, chondrogenic, and myogenic cell lineages . 

These cells additionally specific CD13, CD29, CD44, CD73, CD90, CD105, CD146 and CD166, however don't specific hemopoietic markers admire CD14, CD34 or CD45

SHED isolated via enzymatic disaggregation (SHED) and outgrowth (o-SHED) by primary culture technique

SHED secretes neurotrophic factor for repair of motor neurons following dental injury and thus it's projected that SHED are often helpful for the treatment of neurodegenerative diseases

STEM CELL FROM APICAL PAPILLA

Stem cells from apical papilla (SCAP) are the cells which may be discovered at the tooth root apex, this tissue is simplest present at some purpose of root development, before the eruption of tooth into the oral cavity

They are able to differentiating into odontoblast cells and convey dentin in vivo

The third molars are normally extracted at constant time as undergoing root formation and thus they'll represent associate degree exceptional supply of dental apical papilla stem cells (DAPSCs) (other than DPSCs and PDLSCs)

SCAP confirmed a significantly greater bromodeoxyuridine uptake rate, range of population doublings, tissue regeneration capability, and quantity of STRO-1–wonderful cells once as compared with DPSCs

They specific mesenchymal markers, that include STRO-1, CD13, CD24, CD29, CD44, CD73, CD90, CD105, CD106 and CD146, and not hematopoietic markers together with CD18, CD34, CD45 or CD150

DAPSCs are capable to create PDL-like, dentin-like, cementum-like, and bone-like tissues

SCAP specific a better level of survivin (anti-apoptotic protein) than DPSCs and are fine for hTERT (human enzyme polymerase that maintains the end length) activity
root apical papilla is probably to play a important role in root formation, additional studies is required to affirm that this halted root development among the minipig wasn't because of hurt of Hertwig's epithelial root sheath (HERS) throughout the removal of the top papilla of that distinctive root apex

SCAPs also are acceptable for cell-primarily based mostly remedy for formation of apex roots.

• Potential Role of SCAP

• In Pulp Healing and Regeneration

• In Replantation and Transplantation

DENTAL FOLLICLE STEM CELL

Dental follicle may be a loose connective tissue derived from ectomesenchymal cells. It surrounds the teeth organ and therefore the growing enamel germ sooner than eruption and plays specific roles throughout enamel development

DFPCs derived from human 1/3 molars tooth are fleetly attached to the social group plates and form a calcified nodules

DFSCs specific CD9, CD10, CD13, CD29, CD44, CD53, CD59, CD73, CD90, CD105, CD106, CD166 and CD271, however no longer haemopoietic markers inclusive  of CD31, CD34, CD45 and CD133
These cells have a capability to provide bone and cementum.

DFSCs had been also found to own the capability to create salivary gland cells and ductal cells.

DFPCs are effortlessly approachable for mobile tradition and feature a better proliferation capability than DPSCs.

DFSCs have the ability to acquire osteogenic, adipogenic, chondrogenic, neural, and cardiomyocytic differentiation in a specific prompted atmosphere.

DFPCs could have a lot of advantages as a somatic cell aid for regenerative cures in dental abnormalities

The observe confirmed that, when ectopic transplantation, these cells will form PDL-like structures with collagen type I strand assemblies. furthermore, the PDL-like structures confirmed expression of periostin, scleraxis, and type XII collagen, indicating the potential of DFSCs to regenerate pdl in vivo

FUTURE DIRECTIONS

Advancement in stem cell is broken or lost teeth are often replaced by the employment of regenerative therapies. 

Similarly, discovery of iPSCs technology has revolutionized complete treatment protocols within the field of dentistry by employing a idea of autologous transplantation

The Food and Drug Administration has enforced strict laws for somatic cell tissue culturing this is often as a result of xenogenic products, appreciate foetal bovine serum, are typically utilized in stem cell-culture medium

There is no obtainable data on the security and effectivity of multipotent stem cells for periodontal regeneration within the clinical setting

Stem cell advance is that the accessibility of regenerative dental kits, which is able to change the dentists the flexibility to deliver somatic cell therapies domestically as a part of routine practice. 

Dentist will very well manage periodontic diseases by exploitation stem cell and scaffold technology 

DPSCs have added  advantage within the field of endodontic wherever, we will develop human dental pulp within the laboratory.

Dental derived stem cells, appreciate DPSCs, SHEDs, DFSCs, and DAPSCs don't seem to be as effective in create periodontic tissues and so it's going to not be value to test them in future clinical trials.

Looking at the continuing clinical trials, it's too early to invest whether or not all therapies supported stem cells can convince be clinically effective

CHALLENGES

Stem cells of dental origin have multiple applications withal there are bound limitations furthermore

Stem/progenitor cells are relatively less potent than embryonic stem cells

Difficulty to identify, isolate, purify and grow these cells systematically in labs

Immune rejection is additionally one among the problems, that need an intensive thought

Researchers still got to grow blood and nerve offer of teeth to create them totally useful

Photo credit: https://www.intechopen.com/books/embryonic-stem-cells-basic-biology-to-bioengineering/embryonic-stem-cells-for-therapies-challenges-and-possibilities 

CONCLUSION

Although stem cell isn't presently obtainable, these approaches might at some point be used as biological alternatives to the artificial materials presently used.

Dental stem cell analysis poses challenges likewise as risks

If we have a tendency to are to comprehend the advantages, meet the challenges, and avoid the risks, stem cell analysis should be conducted beneath effective, responsible systems of social-responsible oversight and management, at each the national and international levels

REFERENCE 

• G. S. Kumar:Orban's Oral Histology & Embryology, 14th Edition, printed: Elsevier India. ISBN: 9788131240335
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367063/ 
• Seyed Hossein Bassir, Wichaya Wisitrasameewong,Justin Raanan,Sasan Ghaffarigarakani,Jamie Chung, Marcelo Freire,Luciano C. Andrada,and Giuseppe Intini: Potential for Stem Cell-Based Periodontal Therapy. J Cell Physiol. 2016 Jan; 231(1): 50–61.doi: 10.1002/jcp.25067
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491285/
• Zhang J, Ding H, Liu X, Sheng Y, Liu X, Jiang C. Dental Follicle Stem Cells: Tissue Engineering and Immunomodulation. Stem Cells Dev. 2019;28(15):986‐994. doi:10.1089/scd.2019.0012
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478630/#__sec3title
• Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: A review of current status and a call for action. J Endod. 2007;33:377–90. 
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653220 
•  Liu J, Yu F, Sun Y, Jiang B, Zhang W, Yang J, Xu GT, Liang A, Liu S. Concise reviews: Characteristics and potential applications of human dental tissue-derived mesenchymal stem cells. Stem cells (Dayton, Ohio) 2015;33(3):627–638.