Generation of bone/cartilage organoids from neural crest cells to regenerate critical-sized periodontal tissue defects.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16993
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Kyoto University
• Principal Investigator: Souta Motoike 京都大学, iPS細胞研究所, 特別研究員(PD) (80881292)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 間葉系幹細胞集塊 / 歯周組織再生 / 軟骨内骨化 / 神経堤細胞

Outline of Final Research Achievements

Previously, we have developed Clumps of mesenchymal stem cells (MSCs) / extracellular matrix (ECM) complexes (C-MSCs), which consisted of cells and self-produced ECM. Moreover, we have generated bone-like tissue from C-MSCs in vitro by mimicking membranous ossification.
Endochondral ossification is resistant to hypoxic or undernutrition environments and can induce vascularization effectively.
In this study, we have generated bone/cartilage organoids from human neural crest cells-derived ectomesenchyme by using chondrogenic induction and our novel method which produces bone-like tissue from C-MSCs. Besides, we transplanted bone/cartilage organoids into immunodeficient rats’ critical-sized periodontal tissue defect model. We have been currently evaluating whether bone/cartilage organoids can regenerate tissue defects effectively via endochondral ossification.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

侵襲性歯周炎や重度歯周炎のように大規模な骨組織破壊に対しては欠損部が血液供給不足によって低酸素・低栄養状態に陥り、移植体の機能が十分に発揮されない可能性がある。
本研究成果から、生体外で骨組織と軟骨組織の混在するオルガノイドを作製することができた。この骨/軟骨複合型オルガノイドの移植は、低栄養状態に抵抗し、軟骨内骨化によって効果的な組織再生を誘導することが可能と予想される。
本研究が遂行された場合、従来治療困難とされてきた大規模な歯周組織破壊に対しても有効な治療成果を獲得することができる。