Dental Stem Cell Therapy: Awareness and Perspective among Indian Orthodontists

Aim: To assess the, awareness of stem cells among Orthodontists in India. Materials and Methods: A cross-sectional, self-modified, validated questionnaire-based, nationwide survey was conducted among practicing Orthodontists and postgraduate students belonging to various colleges in India. A total of 502 participants completed the questionnaire. Google Form link was generated and circulated. Data were imported in


INTRODUCTION
In a major breakthrough in 1908, Russian histologist Alexander Maksimov proposed the term "stem cell" for scientific usage [1]. Stem cells are defined as clonogenic cells capable of both self-renewal and multi-lineage differentiation. The breakthrough in dental history was achieved in 2000 when Gronthos et al. identified and isolated odontogenic progenitor population in the adult dental pulp. [2] These cells were referred to as dental pulp stem cells (DPSCs). Since this discovery, several researchers have reported varieties of dental stem cells, which include: DPSCs (Dental pulp stem cells)  SHED (stem cells from human exfoliated deciduous teeth)  SCAP (Stem cells from apical papilla)  PDLSCs (Periodontal ligament stem cells) [3] Most researches are directed toward the regeneration of damaged dentin, pulp, resorbed root, periodontal regeneration, and to repair perforations. Whole tooth regeneration to replace the traditional dental implants is also in pipeline. [4] Stem cells (SCs) have been extracted from various organs including muscle, dermis, bone marrow, adipose tissue, periosteum, blood, umbilical cord, synovial membrane, and teeth [5,6]. Research evidence states the application of stem cells in Orthodontics and cranio-facial Orthopedics. The applications are common towards correcting dentofacial anomalies, regeneration of hard (alveolar cleft) and soft tissues (hemifacial microsomia) [7]. As the extraction of primary teeth or permanent premolar or wisdom teeth are common intervention in Orthodontic treatment of malocclusions, SCs sources from the teeth could be gained without extra morbidity [8] Future application of SCs in Orthodontics could involve accelerating tooth movement, regenerating resorbed roots, and expanding tooth movement limitations [9,10,11]. Unfortunately, evidences on the knowledge of the Orthodontists and post graduate students about these have been reported to be weak. [12] This hinders the practice of adopting stem cell for treating the problems using these technologies. Hence, there is a need to educate the Orthodontists and post graduates about the applications of SCs in the field of Orthodontics.
This could only be possible if we know the existing levels of knowledge, attitude and practices of the Orthodontists and post graduates.
Thus, the focus of our survey was to assess knowledge, awareness and perception about stem cell therapy among Orthodontists and by doing so we intend to establish a rationale behind its use. We have also explicated as to why Orthodontists despite being intrigued have dithered the use of stem cell therapy in their practice.

RESULTS
A total of 502 participants completed the questionnaire. Maximum participants belonged to southern India (36.1%). The majority of the participants had an experience of 0-5 years (39.0%) and pursued private practice (27.3%).
The gender distribution was almost at par with 49.8% males and 50.2% females.
The source of knowledge was internet for 72% and 49% obtained from books and journals. The postgraduates predominantly resorted to internet for information. Most Orthodontists (63.7%) and postgraduates (91.2%) reported that they did not attend any conferences related to stem cell applications in Orthodontics. It was seen that 70.6% of the Orthodontists and 37.7% of the postgraduates knew the characteristics of the stem cells. It was reported that 69.6% of Orthodontists and 43.9% of postgraduates were aware that dental stem cells could be a second chance for those who did not bank their cord stem cells. It was reported by 66.8% of Orthodontists and 37.7% of postgraduates that they knew that dental stem cells can be used for the regeneration of tooth, root, bone, and PDL. Orthodontists (37.6%) and postgraduates (34.2%) reported knowing that stem cell therapy produces autoimmune reactions even if it's from your own body. Most of the postgraduates (14.4%) and Orthodontists (24.6%) reported that the ideal source of obtaining stem cells was primary molars and wisdom tooth. It was seen that Orthodontists (70.1%) and postgraduates (43.0%) reported that dental stem cells can be derived from periodontal ligaments, dental ligament, pulpal tissues etc. Significant differences were observed between both groups for the entire variable (  1%). When asked about recommending to patients, the postgraduates ranked higher (95.6%) than that of Orthodontists (88.4%). Statistically significant differences were observed with regard to advising patients regarding stem cell and the various obstacles faced. Mann Whitney U test has been used to find the differences between the groups (Table  3).

DISCUSSION
Stem cells have been used for correcting various craniofacial abnormalities, in distraction osteogenesis, and also in correcting temporomandibular joint anomalies. Recently, it has gained an enormous momentum and hence the need arises to report the level of awareness among various groups of Dentists throughout the Indian subcontinent. The present study aimed to assess the knowledge, awareness, and recommendations of the practicing Orthodontists and postgraduates about application in the field of Orthodontics, stem cell isolation and preservation. A positive interest has been cultivated among dentists which highlight the need to improve the stem cell-related knowledge among the post-graduate students and the practicing orthodontists which would improve their practice and benefit the patients in the long run. There is a paucity of data towards the assessment of knowledge, awareness, and attitude of Orthodontists directing the need for researching this area of interest.

*Significant scores
The level of knowledge appertain to application of stem cells in Orthodontics in the present study was found to be (57%) among postgraduates and (65%) among Orthodontists. In a study conducted by Goswami et al (2019) the level of knowledge was 72%. In the present study, the years of experience were recorded and it was seen that increased years of experience was related to the improvement in knowledge domain scores and post graduates showed a fair knowledge score compared to good knowledge score in that of the Orthodontist. For the Orthodontists, the source of information included conferences, books, and journals while the main source of information was the internet and curriculum books for the post-graduate students.
Thus it could be substantiated that postgraduates would only have higher knowledge if it is inculcated in their curriculum and Orthodontists have exposure to varied journal proceedings, conferences, and also clinical experiences that improve their knowledge.
Isolation and potential harvesting of the dental stem cells are evident from primary (SHED) and permanent pulpal tissues and also from those of impacted and therapeutically extracted teeth. [13][14][15]. The cells from the periodontal ligament, apical papilla of erupted permanent teeth, developing dental follicle also serve as sources of dental stem cells [12]. The overall awareness scores ranked higher. Comparisons were made with other studies where it was reported that the majority of the respondents were aware of the potential sources of the stem cells; (81%) in the study conducted by Goswami et al., 69.6% and 60.3% as reported by Goyal et al, [12,16] Agewise comparisons were made among the study population and it was seen that with an increase in age the positive response increased [17].
Banking of stem cells involves extraction, processing, and storage of dental stem cells for future endeavors. Various storage methods are being used. Education of dental stem cells would not only involve the sources, it should also involve the stem cell harvesting methods along with the techniques of identification.
The current study showed that the postgraduates were more towards adapting newer techniques as compared to the practicing Orthodontists.
Hence, this positive attitude should be encouraged through conferences, CDE programs on stem cells, and academic inclusions to benefit a majority of the population.
The constraints of our study are that it's solely based on the responses of the participants, and it could be subjected to response bias. A clinical intervention to improve the validation of the responses would have been a better alternative.

CONCLUSION
This is a nationwide survey to determine the knowledge, attitude, and practice of Postgraduates and Orthodontists towards application of stem cells in treating Dental, craniofacial anomalies and to facilitate Orthodontic interventions. A varied response was noted among the Orthodontists and post graduates throughout the country.
Results suggest that there is equitable knowledge among all the participants towards stem cell applications recommending the need to educate them about the applications of stem cell in the field of Orthodontics. Comparatively lesser scores have been reported by the postgraduates in the knowledge and awareness domains. The present study recommends the need to incorporate the stem cell topic into the academic curriculum for better clinical performance of the dental specialists this would encourage more of in vivo studies to improve the efficaciousness of treatment rendered to the patients and in turn improve their quality of living.

DISCLAIMER
The products used for this research are commonly and predominantly use products in our area of research and country. There is absolutely no conflict of interest between the authors and producers of the products because we do not intend to use these products as an avenue for any litigation but for the advancement of knowledge. Also, the research was not funded by the producing company rather it was funded by personal efforts of the authors.

CONSENT
As per international standard or university standard, Participants' written consent has been collected and preserved by the author(s).

ETHICAL APPROVAL
The Institutional Ethics Board (147/IRB-IBSEC/SIS) clearance was obtained and the study follows Helsinki Ethics Code 2014.

COMPETING INTERESTS
Authors have declared that no competing interests exist.