Treatment of bone defects using cartilaginous particles produced from human-induced pluripotent stem (iPS) cell derived expandable limb bud mesenchymal cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20991
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Okayama University
• Principal Investigator: Yorimitsu Masanori 岡山大学, 医歯薬学域, 講師 (70907930)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 骨欠損 / iPS細胞 / 軟骨前駆細胞 / 内軟骨性骨化

Outline of Final Research Achievements

Professor Takeshi Takarada, a collaborator on this study, previously developed a protocol for producing expandable limb-bud-like mesenchymal cells that express high levels of Paired related homeobox 1 (PRRX1), have high chondrogenic differentiation potential from human-induced pluripotent stem (iPS) cells, and can be expanded cultured.The bone defect model of SCID rats was created and filled with hyaline cartilaginous-like tissue prepared from this expandable limb-bud-like mesenchymal cells. Evaluation of images over time and histological evaluation of the harvested bone revealed progressive osteogenesis, enchondral ossification, and replacement with autologous bone. In addition, expandable limb-bud-like mesenchymal cells-derived hyaline cartilaginous-like tissue prepared in a medium containing high amounts of BMPs and TGFβ was found to promote osteogenesis.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

開放骨折などの外傷や、骨腫瘍・骨髄炎に対する治療としての切除により、大腿骨などの長管骨の骨欠損がしばしば発生する。骨欠損に対する治療としていくつかの治療法があるが、いずれも採骨部の変形や疼痛、感染、神経血管障害などの合併症のリスクがある上、治療可能距離に限界がある。今回の方法に基づき骨欠損に対して内軟骨性骨化を誘導し治療することができれば、低侵襲で簡便な治療法となり、患者負担の軽減、入院・治療期間の短期化、治療費用の軽減、社会復帰の早期化が達成できる。