Bone regeneration using human induced pluripotent stem cell-derived mesenchymal stem cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10967
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Showa University
• Principal Investigator: Lee Sang Yang 昭和大学, 医学部, 講師 (40533732)
• Co-Investigator(Kenkyū-buntansha): 新倉 隆宏 神戸大学, 医学研究科, 准教授 (40448171) ; 福井 友章 神戸大学, 医学部附属病院, 特定助教 (50437688)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 骨再生 / iPS細胞 / 間葉系幹細胞 / 軟骨分化 / 軟骨内骨化

Outline of Final Research Achievements

We investigated whether implantation of chondrogenically differentiated human iPSCs-derived mesenchymal stem cells (iMSCs) could lead to bone regeneration of bone defects in mice. A 2-mm defect was created at the radius of nude mice. Chodrogenically differentiated iMSC pellets were then implanted in the defect. At week 8, 18 out of 21 (86%) radius in the treated group achieved bone healing, whereas 2 out of 11 (18%) radius in the control group achieved bone healing. At week 8, hitology revealed complete bone union in te treated group. At week 4, hypertrophic chondrocytes transitioning to the newly formed bone indicated that endochondral ossification was involved.
Our results for the first time demonstrated that grafting bone defects with chondrogenically differentiated iMSCs led to successful bone regeneration through endochondoral bone ossification. Our therapy could be a novel system to repair large bone defects.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

本研究によって、軟骨分化させたiMSCの細胞移植が、難治性骨折・骨欠損において、優れた再生能を有することが明らかとなった。本研究結果は、ヒトiPS細胞を用いた骨再生医療の将来の臨床応用の際の重要な情報となりうる。ヒトiPS細胞を用いた骨再生療法に関する知見が大きく広がり、ひいてはiPS細胞を用いた安全で確実な骨再生療法の実現への一歩となることが期待される。