Development of periodontal tissue regenerative therapy by using neural crest-derived MSCs and cell clumps culture technique

• Project/Area Number: 18H02977
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Hiroshima University
• Principal Investigator: Kurihara Hidemi 広島大学, 医系科学研究科(歯), 名誉教授 (40161765)
• Co-Investigator(Kenkyū-buntansha): 加治屋 幹人 広島大学, 医系科学研究科(歯), 助教 (00633041) ; 池谷 真 京都大学, iPS細胞研究所, 准教授 (20442923) ; 水野 智仁 広島大学, 病院(歯), 講師 (60325181) ; 藤田 剛 広島大学, 医系科学研究科(歯), 准教授 (80379883)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: 間葉系幹細胞集塊 / C-MSCs / 神経堤細胞由来間葉系幹細胞 / iPS細胞 / 立体複合化

Outline of Final Research Achievements

By using bone marrow (BM)-derived mesenchymal stem cells (MSCs) and self-produced extracellular matrix (ECM), three-dimensional clumps of MSCs/ECM complexes (C-MSCs) were established. C-MSCs can be transplanted into a defect area with no artificial scaffold to induce tissue regeneration.
Since there is a fact that craniofacial tissues, including such as periodontal tissue, are originated from neural crest cells (NCC)-derived MSCs, NCC-MSCs can be a better candidate for the periodontal tissue regenerative cell therapy compared to BM-MSCs. Accordingly, in this present study, we aimed to establish novel promising periodontal tissue regenerative therapy by using NCC-MSCs and the cell clumps culture technique.

Academic Significance and Societal Importance of the Research Achievements

神経堤細胞は第4の胚葉と呼ばれるほどの多分化能を有し、歯周組織の起源となる細胞であるため、歯周組織再生療法にとって最適な細胞といえる。しかし、発生期のごく限られた時期にのみ見られる細胞であるため、患者から分離して利用することは難しい。
そこで本研究では、iPS細胞から誘導した神経堤細胞由来MSCsを樹立し、さらにその細胞性質を適切に発揮させるために、研究代表者らの独自技術である細胞集塊培養技術を応用した細胞治療法の開発を行った。本研究成果は、これまでにない効果的な歯周組織再生療法の実現につながる可能性がある。

Research Products

• [Journal Article] Cox2-mediated PGE2 production via p38/JNK-c-fos signaling inhibits cell apoptosis in 3D floating culture clumps of mesenchymal stem cell/extracellular matrix complexes (2020)
  • Author(s): Komatsu Nao、Kajiya Mikihito、Morimoto Shin、Motoike Souta、Yoshii Hiroki、Iwata Tomoyuki、Ouhara Kazuhisa、Matsuda Shinji、Mizuno Noriyoshi、Kurihara Hidemi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 530 Issue: 2 Pages: 448-454
  • DOI: 10.1016/j.bbrc.2020.05.100
  • Peer Reviewed / Open Access
• [Journal Article] Clumps of Mesenchymal Stem Cell/Extracellular Matrix Complexes Generated with Xeno-Free Conditions Facilitate Bone Regeneration via Direct and Indirect Osteogenesis (2019)
  • Author(s): Motoike Souta、Kajiya Mikihito、Komatsu Nao、Horikoshi Susumu、Ogawa Tomoya、Sone Hisakatsu、Matsuda Shinji、Ouhara Kazuhisa、Iwata Tomoyuki、Mizuno Noriyoshi、Fujita Tsuyoshi、Ikeya Makoto、Kurihara Hidemi
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 16 Pages: 3970-3970
  • DOI: 10.3390/ijms20163970
  • Peer Reviewed / Open Access
• [Journal Article] Glycyrrhizic acid suppresses inflammation and reduces the increased glucose levels induced by the combination of Porphyromonas gulae and ligature placement in diabetic model mice (2019)
  • Author(s): Akutagawa Keiichi、Fujita Tsuyoshi、Ouhara Kazuhisa、Takemura Tasuku、Tari Misako、Kajiya Mikihito、Matsuda Shinji、Kuramitsu Shohei、Mizuno Noriyoshi、Shiba Hideki、Kurihara Hidemi
  • Journal Title: International Immunopharmacology Volume: 68 Pages: 30-38
  • DOI: 10.1016/j.intimp.2018.12.045
  • Peer Reviewed / Open Access