iPS細胞由来の間葉系間質細胞が発生経路によって異なる性質を持つことを解明~疾患や組織に応じた最適な細胞供給への期待~

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2026-01-07 京都大学 iPS細胞研究所

京都大学iPS細胞研究所(CiRA)の池谷真准教授らの研究グループは、ヒトiPS細胞から5つの異なる発生経路(頭部神経堤、体幹部神経堤、体節、側板中胚葉、肢芽間葉)を経て誘導した間葉系間質細胞(iMSC)の性質を体系的に比較した。その結果、すべてのiMSCが標準的MSCの定義を満たす一方、誘導に用いた発生経路の違いにより、形態、増殖速度、分化能に明確な差があることが明らかになった。体節由来iMSCは骨・軟骨分化に、肢芽間葉由来は脂肪分化に、頭部神経堤由来は肥大化しにくい硝子軟骨形成に適していた。網羅的遺伝子発現解析でも、発生経路を反映したクラスター形成が確認された。本成果は、疾患や治療対象組織に応じて最適なiMSCを選択・供給する再生医療の実現に重要な指針を与える。

iPS細胞由来の間葉系間質細胞が発生経路によって異なる性質を持つことを解明~疾患や組織に応じた最適な細胞供給への期待~
図1. iMSCを誘導する5つの発生経路 (PN4, 4回継代後の細胞)

<関連情報>

胚性系統特異的iPSC由来間葉系幹/間質細胞は、異なる形態と固有の機能を示す Embryonic lineage-specific iPSC-derived mesenchymal stem/stromal cells exhibit different morphologies and intrinsic functions

Linh Nguyen ∙ Souta Motoike ∙ Denise Zujur ∙ … ∙ Junya Toguchida ∙ Hidetoshi Sakurai ∙ Makoto Ikeya
iScience  Published:December 17, 2025
DOI:https://doi.org/10.1016/j.isci.2025.114482

Highlights

  • iMSCs were differentiated from the same iPSC line via 5 different embryonic origins
  • Different iMSC types displayed different intrinsic characteristics
  • Somite-derived iMSCs (SM-iMSCs) showed higher osteogenic differentiation potential
  • Cranial neural crest-derived iMSCs (cNCC-iMSCs) have more chondrogenic potential

Summary

Mesenchymal stem/stromal cells (MSCs) have great potential in regenerative medicine owing to their multilineage differentiation capacity. However, tissue-derived MSCs (tMSCs) exhibit inconsistent characteristics. Although induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) are a potential solution, the effect of different embryonic lineages on their properties remains unknown. We generated MSCs from human iPSCs via five lineage-specific routes: cranial neural crest, trunk neural crest, paraxial mesoderm (somite), lateral plate mesoderm, and limb mesenchyme. All types met established MSC criteria yet differed in morphology, proliferation, and differentiation capacity. Somite-, cranial neural crest-, and limb mesenchyme-derived MSCs showed higher osteogenic potential, whereas somite-derived MSCs also showed high chondrogenic potential but were prone to hypertrophy. Limb mesenchyme-derived MSCs showed the highest adipogenic potential. Transcriptomic profiles indicated distinct clusters within iMSCs. Despite variances, a high correlation level existed between iMSCs and tMSCs. Therefore, iMSCs are potential alternatives to tMSCs in regenerative medicine.

細胞遺伝子工学
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