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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 12  |  Issue : 5  |  Page : 27-36  

Regenerative capacity of dental pulp stem cells: A systematic review


1 Department of Oral and Maxillofacial Pathology and Oral Microbiology, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India
2 Department of Oral Pathology, Sree Anjaneya Institute of Dental Sciences, Kozhikode, Kerala, India; Department of Stem Cells and Regenerative Medicine, Sree Anjaneya Institute of Dental Sciences, Kozhikode, Kerala, India
3 Department of Operative Dentistry and Endodontics, CSI College of Dental Sciences and Research, Madurai, Tamil Nadu, India

Date of Submission04-Feb-2020
Date of Decision06-Mar-2020
Date of Acceptance13-Mar-2020
Date of Web Publication28-Aug-2020

Correspondence Address:
Gururaj Narayana Rao
90/57 Gopala Kothan Street, Madurai, Tamil Nadu.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpbs.JPBS_121_20

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   Abstract 

Objectives: The dental pulp contains undifferentiated mesenchymal cells, blood vessels and so on, which are responsible for routine functions of a tooth. The determination of stemness and regenerative properties using biomarkers and further application in routine practice may unravel its potential. Materials and Methods: Inclusion criteria—original research articles published in English, from 2000 to 2019, were collected both manually and by electronic search from databases of Cochrane, Medline, Embase, and PubMed. Exclusion criteria—articles other than English and review manuscripts were omitted. The shortlisted articles were reviewed for specific biomarkers, to assess the regenerative potential, stemness, and lineage of dental pulp stem cells. Results: Of 512 articles, 64 were selected and reviewed to determine the mesenchymal, neurogenic, vasculogenic, hematopoietic, and stem cell potential. On the basis of the search analysis, a panel of markers was proposed. Conclusion: The application of proposed markers, on a pulpectomized tissue derived from human teeth, may be helpful to determine the regenerative potential and the usefulness in regenerative medicine and tissue engineering.

Keywords: Biomarkers, dental pulp stem cells, regenerative medicine, stem cells, tissue engineering


How to cite this article:
Rosaian AS, Rao GN, Mohan SP, Vijayarajan M, Prabhakaran RC, Sherwood A. Regenerative capacity of dental pulp stem cells: A systematic review. J Pharm Bioall Sci 2020;12, Suppl S1:27-36

How to cite this URL:
Rosaian AS, Rao GN, Mohan SP, Vijayarajan M, Prabhakaran RC, Sherwood A. Regenerative capacity of dental pulp stem cells: A systematic review. J Pharm Bioall Sci [serial online] 2020 [cited 2020 Sep 20];12, Suppl S1:27-36. Available from: http://www.jpbsonline.org/text.asp?2020/12/5/27/292812




   Introduction Top


Dental pulp is a type of unique connective tissue that has an anatomical architecture closely restricted by its location within a rigid chamber of tooth. The dental pulp consists of cellular, noncellular components, collagen, and fibrillin fibers. The nonfibrous components include substances that are derived from the extracellular matrix, mainly glycosaminoglycan, proteoglycans, and other adhesion molecules. This matrix plays a pivotal role in the development, migration, division, shape, and function of the tissue. The presence of blood vessels and nerves plays an important role in the physiological functions of the tooth. It has varied functions ranging from detecting stimuli and also initiating and participating in response against insult.[1] Their regenerative capacity is explained on the basis of presence of various cellular constituents of the dental pulp, which includes odontoblasts, fibroblasts, defense, and undifferentiated cells.[2] The undifferentiated group of cells present in pulp tissue comes under the category of postnatal stem cells. Stem cells are seen in the pulp tissue of both adults and children, within the superficial cell-rich zone, underneath the Hoehl’s cell layer. They are believed to originate from the neural crest cells and segregate into different cell types.[3],[4]

Dental pulp stem cells (DPSCs) are desirable for their unique properties to differentiate into various cell types, which include dentin-producing odontoblasts, neural predecessor cells, chondroblasts, endothelium formative cells, lipocytes, myoblasts, and osteoblasts.[3] DPSCs are mesenchymal cells that constitute one of the most broadly researched cells. Earlier studies have proved that DPSCs can form tissues such as dentin, pulp, and periodontal ligament fibers. These are proved to be a potential stem cell source for orthopedic and orofacial restoration, and it is postulated that these cells may contribute beyond the stomatognathic system.[4]

Regenerative potentials of the dental pulp tissue have been established in various fields such as, cure of neuro-deficit disorders,[5] cardiac-related disorders,[6] muscular disorders (muscular dystrophy),[7] genetic and lifestyle disorders,[8] liver diseases, ophthalmic-related defects,[9] immune diseases, diseases related to the orofacial, bone defects,[10] and infertility treatments. Hence based on the aforementioned facts, systematic review in DPSC was undertaken, which includes various biomarkers having regenerative potential and lineage, and with probable clinical applications were identified.


   Materials and Methods Top


This review was carried out based on the standard guidelines for making of a systematic review (Prisma Guidelines 2015) [Figure 1].[11]
Figure 1: PRISMA diagram

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Eligibility criteria

Inclusion criteria: Original research articles published in English in the year from 2000 to 2019 and related to the title were selected for the review.

Exclusion criteria: Articles other than English language and review manuscripts were excluded. The stem cell markers and regenerative markers were the main method of determination of the potentiality of the dental pulp tissue.

Sources, search strategy, and study selection

Various standardized search engines were used, such as PubMed, Cochrane Library, Embase, and Medline. In addition, a manual search was performed on the personalized collection of journals.

Two oral pathologists reviewed the articles and an experienced reviewer specialized in stem cell gave final decision.


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   Discussion Top


The dental pulp is an intricate tissue that has got multiple potentials and functions to protect the pulp against challenges such as caries or dental trauma. Michael Goldberg[12] had earlier proposed that the knowledge of the inbuilt defense mechanisms employed by the dental pulp has given similar ideas to induce pulp regeneration therapeutically. Ingle’s has observed that multiple growth factors act as important controllers in the instigation of each of the phases of tooth development.[13] This supports the idea of regenerating an entire dentine–pulp complex from the dental pulp tissue itself.

Though earlier studies have been conducted regarding its regenerative potential, a proper categorization of the stem cells derived has not been made.[14] Hence review has been formulated on the following three criteria:

  • (1) To determine the maximum number of immunohistochemical markers that were used in determining the potency of the pulpal tissue


  • (2) To categorize the markers based on the respective properties such as mesenchymal, multi-lineage potency, vasculogenic, neurogenic, osteogenic, musculogenic, dentinogenic, and hematopoietic, thereby confirming the pluripotent nature of the pulpal tissue


  • (3) To derive a standardized protocol of panel of markers.


Markers used by various authors and its application in the pulp are systematically analyzed in this review [Table 1].[77] On the basis of the results, the multi-lineage potency of the dental pulp tissue predicted by various markers has been tabulated [Table 2].
Table 1: The type of markers used by various authors and the interpretations derived[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72],[73],[74],[75],[76],[77],[78]

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Table 2: Pluripotency, markers, and number of articles

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A panel of markers is proposed based on the markers used frequently by different authors, which shows the multi-lineage capacity and to support our aim of this review [Table 3].
Table 3: Proposed markers as investigation protocol for stemness and regeneration

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   Conclusion Top


DPSC has a multi-lineage capacity, proved by various studies. The pulp tissue, which is considered as biological waste following extraction and endodontic treatment, can be harvested for the study. DPSC being mesenchymal and neuroectodermal origin has great potency for various therapeutic and regenerative purposes. It is imperative to study about this tiny tissue and its potential. On the basis of our review, we suggest that preservation of dental pulp tissue and subjecting them to the panel of biomarkers such as CD146, CD 73, CD 105, STRO-1, and SOX-2 will unravel its regenerative potential and lineage. The limitation of this analysis is that the panel of markers proposed is yet to apply practically in a pulp tissue to confirm its viability.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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