Tooth for a tooth: Tissue engineering made easy at dental chairside.

BACKGROUND: Stem cells are unspecialized, multipotent cells which can differentiate into different cell types. The human periodontal ligament encloses subpopulation of Periodontal Ligament Stem Cells (PDLSCs) which are able to regenerate the periodontium by differentiating into various cells of PDL. Literature have shown the promising results of periodontal regeneration by exvivo cultured transplantation of PDLSCs into the osseous defects.
METHODS: Based on current literature on use of ex vivo culture and associated problems, a novel technique is being presented , Stem cell application in periodontal regeneration (SAI-PRT) which uses autologous PDLSCs along with its niche adhering to extracted tooth root for direct application using gelatin sponge as scaffold in regeneration of intrabony periodontal defect bypassing ex-vivo culture.
RESULTS: The cases initiated under SAI-PRT protocol, and have shown excellent clinical and radiographic improvement in intrabony defect using direct transplant of autologous PDLSCs .
CONCLUSIONS: SAI-PRT can be used for the treatment of periodontal osseous defects at chair side.

INTRODUCTION

Mesenchymal stem cells are originally derived from bone marrow, which are spindle-shaped and process the characteristics of multipotential differentiation.[1] In physiologic terms, the Mother Nature has been kind to replace those cells and tissues which wear out on and off throughout the life of living beings. The gift of nature, stem cells are usually processed and expanded in culture through various laborious sensitive steps in the laboratory to prepare the transplant which is transferred to a required donor site.

The three main principles of tissue engineering are scaffold, growth differentiation signals, and stem cells.[2] The contribution of stem cell niche is discussed pertinent to stem cell proliferation in the following paragraph.

STEM CELL NICHE CONCEPT

“Stem-cell” populations are located in “niches” – which are specific for anatomic location which controls the participation of stem cells in tissue regeneration, maintenance, and repair. It controls physiologic proliferation as well as protects the host from over exuberation. It is the basic unit of physiology which maintains the stem cells in a balanced state by providing integrating signals according to the need of the organisms. However, sometimes, it may induce pathologies by its aberrant functions. The crosstalk between stem cells and their niche provides a dynamic environment which is necessary for the sustaining tissue and for the stem cell therapeutics. The niche is not just the location of stem cells, but it must have both anatomic and functional dimensions.[3] Periodontal ligament stem cells (PDLSCs) are present in the soft tissue adherent to extracted tooth root[4] and in the paravascular area.[5] The PDLSC along with its microenvironment can be referred as PDLSC niche.

As of now, PDLSC niche is less explored than the other niches in the body. At present due to growing interest in periodontal regeneration therapy, periodontal niche requires to be explored by the scientist for the beneficial effect. The presence of PDLSCs with its microenvironment in the soft tissue adherent to extracted tooth root can be regarded as “PDLSC niche.” The current study utilized this PDLSC niche for periodontal regeneration.

So far, the niche concept was never there in limelight. However, in 1978, stem cell concept has gained experimental support, which was first supported by Schofield.[6] The crosstalk between different cell types within the stem cell niche provides an opportunity to cell communication and controls the physiologic activity of normal stem cells to boost their ability to respond to therapeutic needs.

The procurement of stem cells for therapeutic purpose from several sources is difficult. Whereas dental stem cells are concerned, especially the PDLSCs are easy to procure and process them. The excellent contribution by Seo et al. 2004[4] on postnatal PDLSCs proved the stem cell location on freshly isolated human PDL, which has the potential to differentiate into cementoblastic/osteoblastic cells in vitro and cementum/PDL-like tissues in vivo.

STEM CELL ASSISTANCE IN PERIODONTAL REGENERATION TECHNIQUE

The priceless contribution of these PDLSCs to form alveolar bone, cementum, and periodontal ligament is discussed in literature. The soft tissue adherent to extracted root contains PDLSCs[4] which was used for PDLSC cell isolation and ex vivo expansion.[78] The safety and efficacy of ex vivo cultured PDLSCs obtained from soft tissue of extracted root is determined by Chen et al.[8] in the phase I trial. These PDLSCs which are in the soft tissue (PDLSC niche) adherent to the extracted tooth root have gone as waste in the bucket after extraction. One such potential of PDLSC niche has been tapped by a dentist couple (authors), an oral and maxillofacial surgeon, and periodontist as their brainchild. A constructive thought process of utilizing the autologous PDLSC niche directly into the bone defect (present in the same person) caused by periodontitis (gum disease) became the first ever venture to elicit the in vivo regenerative activity of PDLSCs successfully in humans without expanding (increasing the number of cells) them in culture and transplant it. The dimension of bone defect caused by gum disease varies from 5 to 7 mm in length and 3 to 2 mm in width or more for which the direct transplantation of PDLSC niche was adequate. Otherwise larger bone defects such as cyst and others may not be right candidates for direct autologous stem cell transplantation as the required number cells may be inadequate that needs to be studied.

The technique of simple direct transplantation of autologous PDLSCs from the extracted root site to another bone defect existing in the same individuals is designated as stem cell. Vandana et al., 2015[9] have reported autologous stem cell application in tissue regeneration technique (SAITRT). The treatment of periodontal osseous defects using the above technique based on tissue engineering triad such as utilisation of autologous periodontal ligament stem cells along with its niche which contains growth factors, and gelatin sponge as scaffold for periodontal regeneration is referred as SAI-PRT(Autologous Stem Cell assisstance in Periodontal Regeneration Technique). This has proved the effect of PDLSCs in 14 cases so far treated. The clinical pocket depth reduction, radiographic density, and bone fill are the measures of success [Figures 1 and 2; pre- and post-operative]. PDLSC niche provided the therapeutic benefit and showed no adverse effects during the entire course of the study.

Figure 1

Radiograph (baseline)

Figure 2

Radiograph at 1-year follow-up

So far, two authors, Feng et al.[7] and Chen et al.,[8] utilized ex vivo cultured autologous PDLSC along with bone graft and guided tissue regeneration membrane. In their study, the probing pocket depth reduction, clinical attachment level, and radiographic improvement are attributed to PDLSCs, bone graft, and GTR. The PDLSC contribution for periodontal regeneration is not able to discriminate.

The basic problem faced during ex vivo cell culture is that the sensitive nature of the procured PDLSC from the extracted tooth root to survive for ex vivo culture. There are several attempts by the researcher to succeed in the stem cell survival as the first step in ex vivo cell culture expansion. Keeping this in mind, the authors of the paper attempted to place the PDLSC niche adherent to the root directly into the debrided osseous defect following extraction of impacted tooth in the same patient. The crucial step of cell survival by direct placement served the best of tissue engineering principle as chairside reality by-passing the ardous laboratory procedure of ex vivo culture and stem cell expansion.

BASIS OF STEM CELL APPLICATION IN PERIODONTAL REGENERATION TECHNIQUE

To date, numerous in vivo studies for periodontal regeneration have utilized ex vivo cultured stem cells which are derived from bone marrow and PDL along with other grafts such as autografts, xenografts, allografts, and alloplastic materials.[10]

The use of autologous PDLSCs niche without ex vivo culture was found to be safe in small-sized periodontal osseous defects. Further, multicenter randomized clinical trials are recommended to allow the clinicians/periodontist to comprehend the easy measures of chairside cell-based periodontal regeneration as a clinical reality.

Stem cell therapy recalls the silent, intentional, highly regular, replacement of worn out cells by the “Mother Nature.” Thanks to the Mother Nature for the thought process to make the BEST of the WASTE and tissue engineering made easy chairside.

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Nil.

Conflicts of interest

There are no conflicts of interest.