Biology:Dental pulp stem cells

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Dental pulp stem cells (DPSCs) are stem cells present in the dental pulp, which is the soft living tissue within teeth. They are pluripotent, as they can form embryoid body-like structures (EBs) in vitro and teratoma-like structures that contained tissues derived from all three embryonic germ layers when injected in nude mice.[1] DPSCs can differentiate in vitro into tissues that have similar characteristics to mesoderm, endoderm and ectoderm layers.[1] DPSCs were found to be able to differentiate into adipocytes and neural-like cells.[2] These cells can be obtained from postnatal teeth, wisdom teeth, and deciduous teeth, providing researchers with a non-invasive method of extracting stem cells.[3] As a result, DPSCs have been thought of as an extremely promising source of cells used in endogenous tissue engineering.[4] Studies have shown that the proliferation rate of DPSCs is 30% higher than in other stem cells, such as bone marrow stromal stem cells (BMSSCs).[5] These characteristics of DPSCs are mainly due to the fact that they exhibit elevated amounts of cell cycling molecules, one being cyclin-dependent kinase 6 (CDK6), present in the dental pulp tissue.[5] Additionally, DPSCs have displayed lower immunogenicity than MSCs.[6]

Atari et al., established a protocol for isolating and identifying the subpopulations of dental pulp pluripotent-like stem cells (DPPSC). These cells are SSEA4+, OCT3/4+, NANOG+, SOX2+, LIN28+, CD13+, CD105+, CD34-, CD45-, CD90+, CD29+, CD73+, STRO1+, and CD146-, and they show genetic stability in vitro based on genomic analysis with a newly described CGH technique.[1]

Role in regenerative dentistry

The human mouth is vulnerable to craniofacial defects, microbial attacks, and traumatic damages.[7] Although preclinical and clinical partial regeneration of dental tissues has shown success, the creation of an entire tooth from DPSCs is not yet possible.[7]

Distraction osteogenesis

Distraction osteogenesis (DO) is a method of bone regeneration, commonly used in the surgical repair of large craniofacial defects.[4] The area in which the defect is present is purposely broken in surgery, allowed to heal briefly, and then the bone segments are gradually separated until the area has healed satisfactorily. A study conducted in 2018 by Song et al. found that DPSCs transfected with Sirtuin-1 (SIRT1) in rabbits were more effective in promoting bone formation during DO.[4] SIRT1-modified DPSCs accumulated significantly higher levels of calcium after osteogenic differentiation in vitro, suggesting the potential role of DPSCs in enhancing the efficiency of DO.[4]

Calcined tooth powder

Calcine tooth powder (CTP) is obtained by burning extracted teeth, destroying the potential infection-causing material within the tooth, resulting in tooth ash [8] Tooth ash has been shown to promote bone repair.[9] Although recent studies have shown that calcine tooth powder- culture media (CTP-CM) does not affect proliferation, they have shown that CTP-CM has significantly increased levels of osteo/odontogenic markers in DPSCs.[8]

Stem cells from human exfoliated deciduous teeth

Stem cells from human exfoliated deciduous teeth (SHED) are similar to DPSCs in the sense that they are both derived from the dental pulp, but SHED are derived from baby teeth, whereas DPSCs are derived from adult teeth. SHED are a population of multipotent stem cells that are easily collected, as deciduous teeth either shed naturally or are physically removed in order to facilitate the proper growth of permanent teeth.[10][11] These cells can differentiate into osteocytes, adipocytes, odontoblast, and chondrocytes in vitro.[11] Recent work has shown the enhanced proliferative capabilities of SHED when compared with that of dental pulp stem cells.[11]

Potential therapeutic use of SHED

Studies have shown that under the influence of oxidative stress, SHED (OST-SHED) displayed increased levels of neuronal protection.[12] The properties of these cells exhibited in this study suggest that OST-SHED could potentially prevent of oxidative stress-induced brain damage and could aid in the development of therapeutic tools for neurodegenerative disorders.[12] After SHED injection into Goto-Kakizaki rats, type II diabetes mellitus (T2DM) was ameliorated, suggesting the potential for SHED in T2DM therapies.[13]

Recent studies have also shown that the administration of SHED in mice ameliorated the T cell immune imbalance in allergic rhinitis (AR), suggesting the cells' potential in future AR treatments.[14] After introducing SHED, mice experienced reduced nasal symptoms and decreased inflammatory infiltration.[14] SHEDs were found to inhibit the proliferation of T lymphocytes, increase levels of an anti-inflammatory cytokine, IL-10, and decrease the levels of a pro-inflammatory cytokine, IL-4.[14]

Additionally, SHED can potentially treat liver cirrhosis.[15] In a study conducted by Yokoyama et al. (2019), SHED were differentiated into hepatic stellate cells.[15] They found that when hepatic cells derived from SHED were transplanted into the liver of rats, liver fibrosis was terminated, allowing for the healing of the liver structure.[15]

History

  • In 2000, a population of odontogenic progenitor cells with high self-renewal and proliferative capacity was identified in the dental pulp of humans permanent third molars.[16]
  • 2005 NIH announces discovery of DPSCs by Dr. Irina Kerkis [17]
  • 2006 IDPSC Kerkis reported discovery of Immature Dental Pulp Stem Cells (IDPSC),[18] a pluripotent sub-population of DPSC using dental pulp organ culture.
  • 2007 DPSC 1st animal studies begin for bone regeneration.[19][20]
  • 2007 DPSC 1st animal studies begin for dental end uses.[21][22]
  • 2008 DPSC 1st animal studies begin for heart therapies.[23]
  • 2008 IDPSC 1st animal study began for muscular dystrophy therapies.[24]
  • 2008 DPSC 1st animal studies begin for regenerating brain tissue.[25]
  • 2008 DPSC 1st advanced animal study for bone grafting announced. Reconstruction of large size cranial bone defects in rats.[26]
  • 2010 IDPSC 1st human trial for cornea replacement

[27]

References

  1. ↑ 1.0 1.1 1.2 Atari, M.; Gil-Recio, C.; Fabregat, M.; García-Fernández, D.; Barajas, M.; Carrasco, M. A.; Jung, H. S.; Alfaro, F. H. et al. (2012). "Dental pulp of the third molar: A new source of pluripotent-like stem cells". Journal of Cell Science 125 (Pt 14): 3343–56. doi:10.1242/jcs.096537. PMID 22467856. 
  2. ↑ Gronthos, S.; Brahim, J.; Li, W.; Fisher, L. W.; Cherman, N.; Boyde, A.; Denbesten, P.; Robey, P. G. et al. (2002). "Stem cell properties of human dental pulp stem cells". Journal of Dental Research 81 (8): 531–5. doi:10.1177/154405910208100806. PMID 12147742. 
  3. ↑ Morsczeck, C.; Reichert, T. E. (2018). "Dental stem cells in tooth regeneration and repair in the future". Expert Opinion on Biological Therapy 18 (2): 187–196. doi:10.1080/14712598.2018.1402004. PMID 29110535. 
  4. ↑ 4.0 4.1 4.2 4.3 Song, D.; Xu, P.; Liu, S.; Wu, S. (2019). "Dental pulp stem cells expressing SIRT1 improve new bone formation during distraction osteogenesis". American Journal of Translational Research 11 (2): 832–843. PMID 30899383. 
  5. ↑ 5.0 5.1 Shi, S.; Robey, P. G.; Gronthos, S. (2001). "Comparison of human dental pulp and bone marrow stromal stem cells by cDNA microarray analysis". Bone 29 (6): 532–9. doi:10.1016/S8756-3282(01)00612-3. PMID 11728923. 
  6. ↑ Ching, H. S.; Luddin, N.; Rahman, I. A.; Ponnuraj, K. T. (2017). "Expression of Odontogenic and Osteogenic Markers in DPSCS and SHED: A Review". Current Stem Cell Research & Therapy 12 (1): 71–79. doi:10.2174/1574888X11666160815095733. PMID 27527527. 
  7. ↑ 7.0 7.1 Amrollahi, P.; Shah, B.; Seifi, A.; Tayebi, L. (2016). "Recent advancements in regenerative dentistry: A review". Materials Science and Engineering: C 69: 1383–90. doi:10.1016/j.msec.2016.08.045. PMID 27612840. 
  8. ↑ 8.0 8.1 Wu, J.; Li, N.; Fan, Y.; Wang, Y.; Gu, Y.; Li, Z.; Pan, Y.; Romila, G. et al. (2019). "The Conditioned Medium of Calcined Tooth Powder Promotes the Osteogenic and Odontogenic Differentiation of Human Dental Pulp Stem Cells via MAPK Signaling Pathways". Stem Cells International 2019: 4793518. doi:10.1155/2019/4793518. PMID 31015840. 
  9. ↑ Morsczeck, C.; Götz, W.; Schierholz, J.; Zeilhofer, F.; Kühn, U.; Möhl, C.; Sippel, C.; Hoffmann, K. H. (2005). "Isolation of precursor cells (PCS) from human dental follicle of wisdom teeth". Matrix Biology 24 (2): 155–65. doi:10.1016/j.matbio.2004.12.004. PMID 15890265. 
  10. ↑ Li, Y.; Yang, Y. Y.; Ren, J. L.; Xu, F.; Chen, F. M.; Li, A. (2017). "Exosomes secreted by stem cells from human exfoliated deciduous teeth contribute to functional recovery after traumatic brain injury by shifting microglia M1/M2 polarization in rats". Stem Cell Research & Therapy 8 (1): 198. doi:10.1186/s13287-017-0648-5. PMID 28962585. 
  11. ↑ 11.0 11.1 11.2 Yao, S.; Tan, L.; Chen, H.; Huang, X.; Zhao, W.; Wang, Y. (2019). "Potential Research Tool of Stem Cells from Human Exfoliated Deciduous Teeth: Lentiviral Bmi-1 Immortalization with EGFP Marker". Stem Cells International 2019: 3526409. doi:10.1155/2019/3526409. PMID 30984268. 
  12. ↑ 12.0 12.1 Xiao, L.; Saiki, C.; Okamura, H. (2019). "Oxidative Stress-Tolerant Stem Cells from Human Exfoliated Deciduous Teeth Decrease Hydrogen Peroxide-Induced Damage in Organotypic Brain Slice Cultures from Adult Mice". International Journal of Molecular Sciences 20 (8): 1858. doi:10.3390/ijms20081858. PMID 30991705. 
  13. ↑ Rao, N.; Wang, X.; Zhai, Y.; Li, J.; Xie, J.; Zhao, Y.; Ge, L. (2019). "Stem cells from human exfoliated deciduous teeth ameliorate type II diabetic mellitus in Goto-Kakizaki rats". Diabetology & Metabolic Syndrome 11: 22. doi:10.1186/s13098-019-0417-y. PMID 30858895. 
  14. ↑ 14.0 14.1 14.2 Dai, Y. Y.; Ni, S. Y.; Ma, K.; Ma, Y. S.; Wang, Z. S.; Zhao, X. L. (2019). "Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro". Stem Cell Research & Therapy 10 (1): 39. doi:10.1186/s13287-019-1134-z. PMID 30670101. 
  15. ↑ 15.0 15.1 15.2 Yokoyama, T.; Yagi Mendoza, H.; Tanaka, T.; Ii, H.; Takano, R.; Yaegaki, K.; Ishikawa, H. (2019). "Regulation of CCL4-induced liver cirrhosis by hepatically differentiated human dental pulp stem cells". Human Cell 32 (2): 125–140. doi:10.1007/s13577-018-00234-0. PMID 30637566. 
  16. ↑ Mantesso, A.; Sharpe, P. (2009). "Dental stem cells for tooth regeneration and repair". Expert Opinion on Biological Therapy 9 (9): 1143–54. doi:10.1517/14712590903103795. PMID 19653863. 
  17. ↑ Miura, M.; Gronthos, S.; Zhao, M.; Lu, B.; Fisher, L. W.; Robey, P. G.; Shi, S. (2003). "SHED: Stem cells from human exfoliated deciduous teeth". Proceedings of the National Academy of Sciences 100 (10): 5807–12. doi:10.1073/pnas.0937635100. PMID 12716973. Bibcode: 2003PNAS..100.5807M. 
  18. ↑ Kerkis, Irina; Kerkis, Alexandre; Dozortsev, Dmitri; Stukart-Parsons, Gaëlle Chopin; Gomes Massironi, Sílvia Maria; Pereira, Lygia V.; Caplan, Arnold I.; Cerruti, Humberto F. (2006). "Isolation and Characterization of a Population of Immature Dental Pulp Stem Cells Expressing OCT-4 and Other Embryonic Stem Cell Markers". Cells Tissues Organs 184 (3–4): 105–16. doi:10.1159/000099617. PMID 17409736. 
  19. ↑ Graziano, Antonio; d'Aquino, Riccardo; Angelis, Maria Gabriella Cusella-De; De Francesco, Francesco; Giordano, Antonio; Laino, Gregorio; Piattelli, Adriano; Traini, Tonino et al. (2008). "Scaffold's surface geometry significantly affects human stem cell bone tissue engineering". Journal of Cellular Physiology 214 (1): 166–72. doi:10.1002/jcp.21175. PMID 17565721. 
  20. ↑ D'aquino, Riccardo; Papaccio, Gianpaolo; Laino, Gregorio; Graziano, Antonio (2008). "Dental Pulp Stem Cells: A Promising Tool for Bone Regeneration". Stem Cell Reviews 4 (1): 21–6. doi:10.1007/s12015-008-9013-5. PMID 18300003. 
  21. ↑ Onyekwelu, O; Seppala, M; Zoupa, M; Cobourne, MT (2007). "Tooth development: 2. Regenerating teeth in the laboratory". Dental Update 34 (1): 20–2, 25–6, 29. doi:10.12968/denu.2007.34.1.20. PMID 17348555. 
  22. ↑ Cordeiro, Mabel M.; Dong, Zhihong; Kaneko, Tomoatsu; Zhang, Zhaocheng; Miyazawa, Marta; Shi, Songtao; Smith, Anthony J.; Nör, Jacques E. (2008). "Dental Pulp Tissue Engineering with Stem Cells from Exfoliated Deciduous Teeth". Journal of Endodontics 34 (8): 962–9. doi:10.1016/j.joen.2008.04.009. PMID 18634928. 
  23. ↑ Gandia, Carolina; Armiñan, Ana; García-Verdugo, Jose Manuel; Lledó, Elisa; Ruiz, Amparo; Miñana, M Dolores; Sanchez-Torrijos, Jorge; Payá, Rafael et al. (2008). "Human Dental Pulp Stem Cells Improve Left Ventricular Function, Induce Angiogenesis, and Reduce Infarct Size in Rats with Acute Myocardial Infarction". Stem Cells 26 (3): 638–45. doi:10.1634/stemcells.2007-0484. PMID 18079433. 
  24. ↑ Kerkis, Irina; Ambrosio, Carlos E; Kerkis, Alexandre; Martins, Daniele S; Zucconi, Eder; Fonseca, Simone AS; Cabral, Rosa M; Maranduba, Carlos MC et al. (2008). "Early transplantation of human immature dental pulp stem cells from baby teeth to golden retriever muscular dystrophy (GRMD) dogs: Local or systemic?". Journal of Translational Medicine 6: 35. doi:10.1186/1479-5876-6-35. PMID 18598348. 
  25. ↑ Nosrat, I; Widenfalk, J; Olson, L; Nosrat, CA (2001). "Dental Pulp Cells Produce Neurotrophic Factors, Interact with Trigeminal Neurons in Vitro, and Rescue Motoneurons after Spinal Cord Injury". Developmental Biology 238 (1): 120–32. doi:10.1006/dbio.2001.0400. PMID 11783998. [failed verification]
  26. ↑ de Mendonça Costa, André; Bueno, Daniela F.; Martins, Marília T.; Kerkis, Irina; Kerkis, Alexandre; Fanganiello, Roberto D.; Cerruti, Humberto; Alonso, Nivaldo et al. (2008). "Reconstruction of Large Cranial Defects in Nonimmunosuppressed Experimental Design With Human Dental Pulp Stem Cells". The Journal of Craniofacial Surgery 19 (1): 204–10. doi:10.1097/scs.0b013e31815c8a54. PMID 18216690. 
  27. ↑ Vishwakarma, Ajaykumar (2014-11-13). Stem Cell Biology and Tissue Engineering in Dental Sciences. Elsevier. ISBN 978-0-12-397157-9. https://books.google.com/books?id=22ipoAEACAAJ. 

Further reading

  • Atari, M.; Gil-Recio, C.; Fabregat, M.; Garcia-Fernandez, D.; Barajas, M.; Carrasco, M. A.; Jung, H.-S.; Alfaro, F. H. et al. (2012). "Dental pulp of the third molar: a new source of pluripotent-like stem cells". Journal of Cell Science 125 (Pt 14): 3343–56. doi:10.1242/jcs.096537. PMID 22467856. 




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