Stem Cells and Their Application in Dentistry: A Review Muraleedhara Bhat, Praveen Shetty, Subramanya Shetty, Faizan A. Khan, Shabeeb Rahman, andMallikarjuna Ragher. J Pharm Bioallied Sci. 2019 May; 11(Suppl 2): S82–S84.

Abstract

The use of the term “stem cells” dates back to the 1800s; however, the application of the same is still not completely understood. Recent advances have indicated the harvesting of postnatal stem cells from sources such as the dental pulp and fat. The pluripotent nature of these cells allows for use in various aspects of treatment and patient care such as organ and tissue transplantation, bony defects repair, distraction osteogenesis, cell therapies, gene therapy, and toxicology testing of new drugs. This article explores the various aspects involved, the current status, and future challenges of stem cell therapy in patient care and management.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555346/

Myriad applications of dental pulp stem cells. Nareshwaran Gnanasegaran

Abstract

Dear Editor, I read the article “Amniotic membrane as a biological scaffold for dental pulp stem cell transplantation in ocular surface reconstruction” by Monteiro et al. with great interest(1). The potential applications of dental pulp stem cells (DPSCs) are limitless-especially regarding corneal regeneration. The study demonstrated that, in the presence of amniotic membrane (AM), the tendency of DPSCs to differentiate is reduced, creating a potential source for eye-related cell therapies. The ease of access and fewer ethical hurdles for using DPSCs has made them very popular in the field of regenerative medicine. Previously, we demonstrated the differentiation potential of DPSCs toward neuron-like cells-especially dopaminergic-like cells(2) and hepatocyte-like cells(3) as well as their immunomodulatory behaviors and paracrine effects(4). It is indeed interesting to see the myriad of application avenues for this cell type despite their origin from such a small amount of tissue. As an advocate of DPSCs, I hope to see them applied for cell therapy one fine day. I agree with the author’s point of view that the use of autologous stem cells relieves us from graft rejection; however, in some circumstances, there is no option but to incorporate allogeneic stem cells with immunosuppressive drugs. Although AM seems to be efficient for promoting the growth of DPSCs, there is a risk of HIV, hepatitis, and other viral infections if the cells are not selected carefully. By targeting genes which are responsible in eliciting immune reactions via gene-editing technology(5), I hope that it will be possible to address this issue and put DPSCs into practice. To conclude, studies exploring the full potential of DPSCs should be supported by the global community of scientists. By working together, we will be able to translate our findings from bench to bedside.

References

REFERENCES

1. Monteiro BG, Loureiro RR, Cristovam PC, Covre JL, Gomes JA, Kerkis I. Amniotic membrane as a biological scaffold for dental pulp stem cell transplantation in ocular surface reconstruction. Arq Bras Oftalmol. 2019;82(1):32-7.

2. Gnanasegaran N, Govindasamy V, Kathirvaloo P, Musa S, Abu Kasim NH. Effects of cell cycle phases on the induction of dental pulp stem cells toward dopaminergic-like cells. J Tissue Eng Regen Med. 2018;12(2): e881-93.

3. Vasanthan P, Gnanasegaran N, Govindasamy V, Abdullah AN, Jayaraman P, Ronald VS, et al. Comparison of fetal bovine serum and human platelet lysate in cultivation and differentiation of dental pulp stem cells into hepatic lineage cells. Biochem Eng J. 2014;15(88):142-53.

4. Bindal P, Ramasamy TS, Kasim NH, Gnanasegaran N, Chai WL. Immune responses of human dental pulp stem cells in lipopolysaccharide-induced microenvironment. Cell Biol Int. 2018;42(7): 832-40.

5. Patmanathan SN, Gnanasegaran N, Lim MN, Husaini R, Fakiruddin KS, Zakaria Z. CRISPR/Cas9 in stem cell research: current application and future perspective. Curr Stem Cell Res Ther. 2018;13(8): 632-44.

Xenotransplantation of human dental pulp stem cells in platelet-rich plasma for the treatment of full-thickness articular cartilage defects in a rabbit model. Yanasse RH, De Lábio RW, Marques L, Fukasawa JT ,Segato R, Kinoshita A, Matsumoto MA, Felisbino SL, Solano B, Dos Santos RR, Payão SLM. Exp Ther Med. 2019 Jun;17(6):4344-4356. doi: 10.3892/etm.2019.7499. Epub 2019 Apr 17.

Abstract

Stem cells in platelet-rich plasma (PRP) scaffolds may be a promising treatment for cartilage repair. Human dental pulp stem cell (hDPSC) subpopulations have been identified to have substantial angiogenic, neurogenic and regenerative potential when compared with other stemcell sources. The present study evaluated the potential of hDPSCs in a PRP scaffold to regenerate full-thickness cartilage defects in rabbits. Full-thickness articular cartilage defects were created in the patellar groove of the femur of 30 rabbits allocated into three experimental groups: Those with an untreated critical defect (CTL), those treated with PRP (PRP) and those treated with stem cells in a PRP scaffold (PRP+SC). The patellar grooves of the femurs from the experimental groups were evaluated macroscopically and histologically at 6 and 12 weeks post-surgery. The synovial membranes were also collected and evaluated for histopathological analysis. The synovial lining cell layer was enlarged in the CTL group compared with the PRP group at 6 weeks (P=0.037) but not with the PRP+SC group. All groups exhibited low-grade synovitis at 6 weeks and no synovitis at 12 weeks. Notably, macroscopic grades for the area of articular cartilage repair for the PRP+SC group were significantly improved compared with those in the CTL (P=0.001) and PRP (P=0.049) groups at 12 weeks. Furthermore, histological scores (modified O'Driscoll scoring system) of the patellar groove articular cartilage in the PRP+SC and PRP groups, in which the articular cartilage was primarily hyaline-like, were significantly higher compared with those in the CTL group at 12 weeks (P=0.002 and P=0.007, respectively). The present results support the therapeutic use of hDPSCs for the treatment of full-thickness articular cartilage defects.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507499/pdf/etm-17-06-4344.pdf

Using Dental Pulp Stem Cells for Stroke Therapy. Gancheva MR, Kremer KL, Gronthos S, Koblar SA. Front Neurol. 2019 Apr 29;10:422.

Abstract

Stroke is a leading cause of permanent disability world-wide, but aside from rehabilitation, there is currently no clinically-proven pharmaceutical or biological agent to improve neurological disability. Cell-based therapies using stem cells, such as dental pulp stem cells, are a promising alternative for treatment of neurological diseases, including stroke. The ischaemic environment in stroke affects multiple cell populations, thus stem cells, which act through cellular and molecular mechanisms, are promising candidates. The most common stem cell population studied in the neurological setting has been mesenchymal stem cells due to their accessibility. However, it is believed that neural stem cells, the resident stem cell of the adult brain, would be most appropriate for brain repair. Using reprogramming strategies, alternative sources of neural stem and progenitor cells have been explored. We postulate that a cell of closer origin to the neural lineage would be a promising candidate for reprogramming and modification towards a neural stem or progenitor cell. One such candidate population is dental pulp stem cells, which reside in the root canal of teeth. This review will focus on the neural potential of dental pulp stem cells and their investigations in the stroke setting to date, and include an overview on the use of different sources of neural stem cells in preclinical studies and clinical trials of stroke

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501465/

Dental pulp stem cells and Bonelike^® for bone regeneration in ovine model.Campos JM, Sousa AC, Caseiro AR, Pedrosa SS, Pinto PO, Branquinho MV, Amorim I, Santos JD, Pereira T, Mendonça CM, Afonso A, Atayde LM, Maurício AC. Regen Biomater. 2019 Feb;6(1):49-59.

Abstract

Development of synthetic bone substitutes has arisen as a major research interest in the need to find an alternative to autologous bone grafts. Using an ovine model, the present pre-clinical study presents a synthetic bone graft (Bonelike^®) in combination with a cellular system as an alternative for the regeneration of non-critical defects. The association of biomaterials and cell-based therapies is a promising strategy for bone tissue engineering. Mesenchymal stem cells (MSCs) from human dental pulp have demonstrated both in vitro and in vivo to interact with diverse biomaterial systems and promote mineral deposition, aiming at the reconstruction of osseous defects. Moreover, these cells can be found and isolated from many species. Non-critical bone defects were treated with Bonelike^® with or without MSCs obtained from the human dental pulp. Results showed that Bonelike^® and MSCs treated defects showed improved bone regeneration compared with the defects treated with Bonelike^® alone. Also, it was observed that the biomaterial matrix was reabsorbed and gradually replaced by new bone during the healing process. We therefore propose this combination as an efficient binomial strategy that promotes bone growth and vascularization in non-critical bone defects.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362823/pdf/rby025.pdf

Amniotic membrane as a biological scaffold for dental pulp stem cell transplantation in ocular surface reconstruction. Babyla Geraldes Monteiro, Renata Ruoco Loureiro, Priscila Cardoso Cristovam, Joyce Luciana Covre, José Álvaro Pereira Gomes, Irina Kerkis. Arq. Bras. Oftalmol. 2019, vol.82, n.1, pp.32-37

Abstract

Purpose:

To evaluate the ability of human immature dental pulp stem cells, which are mesenchymal stem cells of neural crest origin, to differentiate into the corneal epithelium for purposes of corneal transplantation and tissue engineering when cultured on de-epithelized amniotic membranes.

Methods:

We compared the immunophenotypes (ABCG2, K3/12, and vimentin) of cells grown on amniotic membranes or plastic surfaces under serum-free conditions or in culture media containing serum or serum replacement components.

Results:

Immature dental pulp stem cells grown on amniotic membranes under basal conditions are able to maintain their undifferentiated state. Our data also suggest that the culture medium used in the present work can modulate the expression of immature dental pulp stem cell markers, thus inducing epithelial differentiation of these cells in vitro.

Conclusions:

Our results suggest that the amniotic membrane is a good choice for the growth and transplantation of mesenchymal stem cells, particularly immature dental pulp stem cells, in clinical ocular surface reconstruction.

http://www.scielo.br/pdf/abo/v82n1/0004-2749-abo-82-01-0032.pdf

Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications. Nakashima M, Iohara K, Bottino MC, Fouad AF, Nör JE, Huang GT. Tissue Eng Part B Rev. 2019 Jan 9.

Abstract

Rapid progress has been made in the last decade related to stem cell-mediated pulp–dentin regeneration, from characterization of dental pulp stem cells (DPSCs) to the first-ever reported clinical case in humans. However, many challenges still need to be addressed before such technology can become a common clinical practice; therefore, further rigorous research is needed. Animal study models are very important to test new ideas, concepts, and technologies. This review summarizes and discusses several key animal models that have been utilized to investigate pulp–dentin regeneration. From a tissue regeneration perspective, we categorize the animal model by the location where the regenerated pulp tissue is formed: ectopic, semiorthotopic, and orthotopic. Several animal species are discussed, including mouse, ferret, dog, and miniswine. Mouse is used for ectopic pulp–dentin regeneration in the dorsum subcutaneous space. A commonly tested approach is hydroxyapatite/tricalcium phosphate (HA-TCP) granules model used to observe ectopic pulp–dentin complex formation. The semiorthotopic model includes tooth slices or fragments with which de novo pulp regeneration in a root canal space can be tested in the mouse subcutaneous space. For orthotopic pulp regeneration, the canine teeth of ferrets are large enough for such purposes. As nonprimate large animal models, dog and miniswine teeth have many aspects quite similar to those of humans, allowing researchers to perform experiments that mimic clinical conditions in humans. The protocols established and the data obtained from large animal studies may directly relate to and apply to future human studies. Complete orthotopic pulp regeneration has been demonstrated in dogs and miniswine. The use of allogeneic and subpopulations of DPSCs for pulp regeneration, and testing of the periapical disease model and aging model have been performed in miniswine or dogs. In sum, all these animal models will help address challenges that still face pulp regeneration in humans. We need to thoroughly utilize these models to test new ideas, technologies, and strategies before reliable and predictable clinical protocols can be established for human clinical trials or treatment.

https://www.liebertpub.com/doi/pdf/10.1089/ten.teb.2018.0194

Pulp Stem Cell-Mediated Functional Pulp Regeneration. Sui B, Chen C, Kou X, Li B, Xuan K, Shi S, Jin Y. J Dent Res. 2019 Jan;98(1):27-35.

Abstract

The preservation of vital dental pulp with vasculature and nerve components remains one of the most significant challenges in modern dentistry. Due to the immense potential for neurovascularization, mesenchymal stem cell (MSC) transplantation has shown emerging promise in regenerative medicine and dental translationalpractice. Actually, pulp mesenchymal stem cells, including postnatal dental pulp stem cells (from permanent teeth) and stem cells from human exfoliated deciduous teeth, possess unique properties based on their origins from neural crest or glial cells. Furthermore, they reside in a neurovascular niche and have the potential for neurogenesis, angiogenesis, and neurovascular inductive activity. According to current pulp regeneration strategies, pulp stem cell-mediated approaches to regeneration have demonstrated convincing evidence that they can rebuild the complex histologic structure of native pulp in situ with highly organized physiologic patterns or even achieve de novo regeneration of complete dental pulp tissues. More importantly, recent clinical studies emphasized in situ neurovascularization outcomes in successful regeneration of vitalized pulp via pulp stem cell transplantation. In this review, we summarize recent breakthroughsin pulp stem cellmediated pulp regeneration, emphasizing the crucial achievement of neurovascularization.

This functional pulp regeneration represents an innovative and promising approach for future regenerative endodontics.

https://www.ncbi.nlm.nih.gov/pubmed/30372659

Artículos científicos año 2019

Stem Cells and Their Application in Dentistry: A Review Muraleedhara Bhat, Praveen Shetty, Subramanya Shetty, Faizan A. Khan, Shabeeb Rahman, andMallikarjuna Ragher. J Pharm Bioallied Sci. 2019 May; 11(Suppl 2): S82–S84.

Abstract

Using Dental Pulp Stem Cells for Stroke Therapy. Gancheva MR, Kremer KL, Gronthos S, Koblar SA. Front Neurol. 2019 Apr 29;10:422.

Dental pulp stem cells and Bonelike® for bone regeneration in ovine model.Campos JM, Sousa AC, Caseiro AR, Pedrosa SS, Pinto PO, Branquinho MV, Amorim I, Santos JD, Pereira T, Mendonça CM, Afonso A, Atayde LM, Maurício AC. Regen Biomater. 2019 Feb;6(1):49-59.

Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications. Nakashima M, Iohara K, Bottino MC, Fouad AF, Nör JE, Huang GT. Tissue Eng Part B Rev. 2019 Jan 9.

Dental pulp stem cells and Bonelike^® for bone regeneration in ovine model.Campos JM, Sousa AC, Caseiro AR, Pedrosa SS, Pinto PO, Branquinho MV, Amorim I, Santos JD, Pereira T, Mendonça CM, Afonso A, Atayde LM, Maurício AC. Regen Biomater. 2019 Feb;6(1):49-59.