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ヒト多能性幹細胞由来肝臓オルガノイドにおける免疫系統の共発達のモデリング

Milad Rezvani1, Susanna Quach2, Kyle Lewis3

  • 1Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, Department of Pediatric Gastroenterology, Nephrology and Metabolic Medicine, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin Institute of Health (BIH) at Charité-Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT)Augustenburger Platz 1, 13353 Berlin, Germany; Berlin Institute of Health, BIH Charité Clinician Scientist Program, 10178 Berlin, Germany; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Der Simulierte Mensch (Si-M), Joint research center of Technische Universität Berlin and Charité - Universitätsmedizin Berlin, Amrumer Str. 33, 13353 Berlin.

Journal of hepatology
|December 19, 2025
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まとめ

ヒト胎児肝臓様オルガノイド（FLO）は、肝臓の発達と免疫細胞の共発達をうまくモデル化しています。この画期的なオルガノイドシステムにより、肝臓の損傷と潜在的な再生療法の研究が可能になります。

キーワード:
胎児肝臓造血ヒト多能性幹細胞免疫肝臓オルガノイド骨髄球形成iPSC

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科学分野:

  • 幹細胞生物学
  • 発生生物学
  • 免疫学

背景:

  • 肝臓の発達には、肝および免疫細胞間の複雑な相互作用が関与しています。
  • 現在のin vitroモデルには、血液の共発達のための内因性ニッチが欠けており、免疫細胞の産出が制限されています。
  • これらの相互作用を研究するには、発達ニッチを再現するモデルが必要です。

研究 の 目的:

  • 多能性造血系を有するヒト胎児肝臓様オルガノイド（FLO）を開発すること。
  • 肝臓の発達と傷害における複雑な多系統相互作用をモデル化すること。
  • 内因性ニッチ内での肝および免疫系統の共発達を調査すること。

主な方法:

  • ヒト多能性幹細胞（hPSC）からのFLOの生成。
  • FLO内での血管形成性間葉および肝内胚葉の共発達。
  • 転写物学、免疫表現型分類、および機能的アッセイによる造血前駆細胞および上皮系統の潜在能力の評価。

主要な成果:

  • FLOは、肝内皮系、間葉系、および多能性造血前駆細胞の出現を支持することに成功しました。
  • 造血および肝系の細胞は、外部要因なしでFLOの微小環境内で成熟しました。
  • FLOは、脂肪肝毒性傷害におけるIL-8媒介性の好中球駆動型傷害応答を明らかにし、肝臓固有の免疫メカニズムを解明しました。

結論:

  • FLOは、造血肝形成および肝臓の自然免疫のための生理学的に関連性の高いモデルを提供します。
  • このシステムは、胎児肝臓の重要な機能を再現し、肝臓の発達および免疫媒介性傷害の研究のためのプラットフォームを提供します。
  • FLOは、小児肝疾患および再生療法の調査のための翻訳ツールとして機能します。