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Geroscience Research Center

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Laboratory of Dental Regenerative Medicine

At the Laboratory of Dental Regenerative Medicine, we restore the function of pulp tissue of teeth with deep cavities or cavities extends to nerves (pulp) and tooth with accumulated pus under the roots forming periapical lesion. We are conducting research on pulp regeneration treatment methods that will have longevity effect for patients.

Currently, it is known that stem cells exist in the bone marrow in bone and many other tissues in the body. The pulp tissue in the tooth contains a lot of stem cells, which are especially beneficial for regenerations blood vessels and nerves, and it is recognized to remove discarded teeth that are not related to occlusion (for convenience with wisdom teeth or orthodontic treatment). Pulp stem cells can be removed from those teeth and can be used for further treatment. Recently, human stem cells have been introduced regarding pulp regeneration treatment method in which pulp stem cells taken out from a patient's own discarded tooth and transplanted into the root canal after the pulp has been removed to restore the functioning pulp of the tooth. This clinical research has been conducted since April 2013 with the approval of the Minister of Health, Labor and Welfare based on the "Guidelines for Clinical Research Used". As a result, it was confirmed that there was no problem with safety in 4 out of 5 cases and the sensitivity of the dental nerve returned within 1 month after the treatment, suggesting that this treatment method was effective.

 

Social significance and usefulness of the desired results

About Laboratory of Dental Regenerative Medicine

Laboratory of Dental Regenerative Medicine is developing new treatments for dental caries and pulpitis.

This research was adopted as one of 24 national projects to promote the development and practical application of advanced medical care as a super special zone in December 2008.

One of the techniques is in the case of "deep dental caries treatment", the dentin is restored by dentin regeneration.

Next, in the case of "treatment of pulpitis in which a part of the pulp is damaged", the pulp function was restored by applying MMP3, which is a kind of enzyme, found on the surface of the pulp to suppress inflammation and regenerate the pulp and even dentin.

Thirdly, in the case of "pulp removal treatment in which pulpitis is severe and the entire pulp must be removed", or in the case of "infected root canal treatment in which pus accumulates under the root", the inner portion of the root (root canal) is cleaned and disinfected. After that, pulp regeneration was done by transplanting "own pulp stem cells" and "cell migration factor" together with "atelocollagen". In the root canal, blood vessels, nerves and pulp are regenerated in a short period of time, and the dentin lid is regeneration at the top, allowing it to return to a living healthy tooth.

Fourth, it is becoming clear that the nanobubble drug introduction method can completely kill bacteria that have invaded deep into the roots of infected root canal teeth in a short period of time. Currently, we are developing a nanobubble generator so that it can be applied to humans.

In particular, regarding the third point of tooth pulp regeneration technology, as an important issue set by the National Council for Science and Technology Policy. In 2010, the "Research and Development System for Accelerating the Practical Use of Health Research Results" of the science and technology strategy promotion, we received the support of experts for the safety and efficacy evaluation of clinical research through the "Program to Support the Elimination of Conflicts". In November 2012, we got approval from the Minister of Health, Labor and Welfare to carry out clinical research on human stem cells, and from April 2013, we conducted 5 clinical studies, and the safety was confirmed and the effectiveness was suggested.

With these technologies, the amount of caries scraped can be minimized and the functions of pulp and dentin can be restored.

In addition, there is no gap for bacteria to invade from the mouth, and it also has a mechanism to prevent tooth decay again. Therefore, it seems to be a technology that helps to make teeth last longer. The technology to produce a large amount of tubule dentin in a short period of time, a drug for treating pulpitis, and the complete regeneration of pulp have not been reported so far, so that it has an international advantage.

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From the laboratory

The National Center for Geriatrics and Gerontology has a mission to promote the independence of the mind and body of the elderly and contribute to the construction of a healthy and longevity society.

Based on that philosophy, Laboratory of Dental Regenerative Medicine conducts innovative dental medicine and its development research aimed at preserving and prolonging the life of teeth.

Specifically, in dental pulpitis or apical periodontitis *, clinical research aimed at "restoring teeth and completely recovering their functions by the world's first new pulp and dentin regeneration treatment method". We performed 5 cases, confirmed the safety, and suggested the effectiveness. This treatment method can be fully applied to middle-aged and elderly people for maintaining the dental health of the elderly. It leads to maintenance of masticatory / communication function, prevention of dementia, maintenance of motor function, etc. We believe that we can contribute to the improvement of living functions of the elderly.

With the cooperation of companies to achieve these goals, the staff of the Research Department will work together on a daily basis with the following goals so that we can deliver dental regenerative medicine to all the people as soon as possible.

  1. We will innovate endodontic treatment (root canal treatment) through dental regenerative medicine and form a base for generalization and dissemination.
  2. Extending the life of teeth and 8020 exercise ** We aim to realize a healthy and long-lived society by increasing the number of achievers.
  3. We aim to realize a healthy and long-lived society through tissue regeneration treatment of blood vessels and nerves using dental pulp stem cells.

notes

  • * Pulpitis or apical periodontitis
    Pulpitis is a condition in which the pulp [nerve of the tooth] inside the tooth is inflamed by stimuli such as caries and trauma.When the pulp is necrotic, inflammation extends beneath the roots and progresses to apical periodontitis. In this case, infected root canal treatment will be performed.Symptoms of pulpitis are sensitivity in the hot or cold water, swelling after eating, and sudden and persistent pain when eating hot.With apical periodontitis, there is pain when chewed or tapped, and there is a persistent, dull pain with a tingling sensation. The swelling of the teeth may cause painful swelling of the lips and cheeks, and the pus may accumulate in the teeth and sometimes crush to produce pus.
  • * * 8020 Exercise (Hachimaru Nimaru Undo)
    It is a dental movement that is being developed in Japan, and its main purpose is to leave more than 20 teeth at the age of 80. It is promoted by the Ministry of Health, Labor and Welfare and the Japan Dental Association. There are many reports that older people with 20 or more teeth are more active and less likely to be bedridden than those with less than 20 teeth. The percentage of people at the age of 80 who have 20 teeth left is currently about 38%, and the Ministry of Health, Labor and Welfare wants to raise it to 50% in 10 years.

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Research achievements

2021

  1. Zayed MH,Iohara K,Watanabe H,Ishikawa M,Tominaga M,Nakahima M Characterization of stable hypoxia-preconditioned dental pulp stem cells compared with mobilized dental pulp stem cells for application for pulp regenerative therapy. Stem Cell Res Ther, 12(1):302, 2021

2020

  1. Nakahima M,Iohara K,Zayed M Pulp Regeneration: Current Approaches, Challenges, and Novel Rejuvenating Strategies for an Aging Population. J Endodontics. 2020;46(9S):S135-S142.
  2. Iohara K,Nakahima M Examination of root canal sterilization effect by drug-containing nanobubble water in intractable apical periodontal disease. 63 (1): 73-82, 2020.
  3. Iohara K,Zayed M,Takei M,Watanabe H,Nakahima M Treatment of Pulpectomized Teeth with Trypsin prior to Transplantation of Mobilized Dental Pulp Stem Cells Enhances Pulp Regeneration in Aged Dogs. Frontiers Bioengineering. 14 August 2020. doi.org/10.3389/fbioe.2020.00983
  4. Zayed MH,Iohara K,Nakashima M Antagonist of CCR3 stimulates pulp regeneration by transplantation of mobilized dental pulp stem cells in aged dog teeth. Scientific Reports. 10, Article number: 8631 (2020)
  5. Azim AA,Iohara K anobubble-Enhanced Antimicrobial Agents: A Promising approach For Regenerative Endodontics. The Journal of Endodontics. 2020 Sep; 46 (9): 1248-1255. Doi: 10.1016 / j.joen.2020.06.002 . Epub 2020 Jun 15.

2019

  1. Nakashima M,Iohara K,Bottino MC,Fouad AF,Nör JE,Huang GT Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications. Tissue Eng Part B Rev. 2019 Apr; 25 (2): 100-113. Doi: 10.1089 / ten.TEB.2018.0194.
  2. Iohara K,Nakashima M Promotion of decalcification effect by nanobubble water-containing EDTA for expansion of closed root canal Journal of the Japanese Society of Conservation of Dentistry 2019 Vol. 62, No. 3, p.152-158.
  3. Iohara K,Nakashima M Examination of the effect of removing the smear layer of a new root canal cleaning solution using nanobubble water, Journal of the Japanese Society of Conservation of Dentistry, 2019, Vol. 62, No. 3, p.159-164.

2018

  1. Ariji Y,Ariji E,Nakashima M,Iohara K Magnetic resonance imaging in endodontics: a literature review. (REVIEW) Oral Radiol. 2018. 34: 10-16. DOI 10.1007 / s11282-017-0301-0
  2. Iohara K,Utsunomiya S,Kohara S,Nakashima M Allogeneic transplantation of mobilized dental pulp stem cells with the mismatched dog leucocyte antigen type is safe and efficacious for total pulp regeneration. Stem Cell Res Therapy.2018 Apr 27;9(1):116.doi: 10.1186/s13287-018-0855-8.
  3. Hayashi Y,Kawamura R,Nishimatu S,Fukuta O,Nakashima M Stem cell induced pulp regeneration can be enhanced by administration of CCL11 neutralizing antibody in the ectopic tooth transplantation model in the aged mice. Rejuvenation Research. 2019; 22 (1) ): 51-59. Doi: 10.1089 / rej.2018.2064.
  4. Okuwa Y,Toriumi T,Nakayama H,Ito T,Otake K,Kurita K,Nakashima M,Honda M Transplanting effects of dental pulp-derived cells on peripheral nerve regeneration in crushed sciatic nerve injury. J Oral Science. 2018 . 60 (4): 526-535.

2017

  1. Miyashita S,Ahmed NE,Murakami M,Iohara K,Yamamoto T,Horibe H,Kurita K,Takano-Yamamoto T, Nakashima M Mechanical forces induce odontoblastic differentiation of mesenchymal stem cells on three -dimensional biomimetic scaffolds. J Tissue Eng. Regen. Med. 2017 Feb; 11 (2): 434-446, 2017. doi: 10.1002 / term.1928. IF 4.428
  2. Nakayama H,Iohara K,Hayashi Y,Okuwa Y,Kurita K,Nakashima M Enhanced regeneration potential of mobilized dental pulp stem cells from immature teeth. Oral Dis. Jul; 23 (5): 620 -628, 2017. DOI: 10.1111 / odi.12619. IF 2.0.
  3. Nakashima M,Iohara K,Murakami M,Nakamura H,Sato Y,Ariji Y,Matsushita K Pulp regeneration by transplantation of dental pulp stem cells in pulpitis: A pilot clinical study. Stem Cell Res Therapy Mar 9; 8 (1): 61, 2017. DOI: 10.1186 / s13287-017-0506-5. IF 4.504.
  4. Nakashima M,Iohara K Recent progress in translation from bench to a pilot clinical study on total pulp regeneration. (REVIEW) J Endod. Sep; 43 (9S): S82-S86. 2017. doi: 10.1016 / j. joen.2017.06.014.

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Award

2020

  1. Iohara K, Nakashima M Investigation of the effect of antibacterial nanoparticle-containing nanobubble water in root canal sterilization in refractory apical periodontitis Japan Journal of Conservative Dentistry Vol. 

2018

  1. Iohara K, Nakashima M Development of a treatment method for promoting pulp regeneration in the elderly by Trypsin pretreatment June 15, 2018 147th Annual Meeting of the Japanese Society of Conservation of Dentistry Cabodental Excellent Poster Award

2017

  1. Iohara K, Fujita M, Ariji Y, Yoshikawa M, Watanabe H, Takashima A, Nakashima M Assessment of pulp regeneration induced by stem cell therapy by Magnetic Resonance Imaging (MRI). The 2017 Journal of Endodontics Awards Apr. 26, 2017.

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