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人iPSC来源晶状体类器官在体外重现晶状体发育与形态发生

Human iPSC-derived lens organoids recapitulate lens development and morphogenesis in vitro

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日本大阪大学等团队在npj Regenerative Medicine发表研究，将人诱导多能干细胞（hiPSCs）的空间图案化自形成外胚层自主多区（SEAM）分化与晶状体优化培养基（LOM）结合，建立体外晶状体形态发生平台。

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npj Regenerative Medicine (2026) Cite this article

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Abstract

The human lens is a transparent, avascular organ essential for focusing light and achieving visual acuity. While animal models have illuminated lens development, direct models of human lens organogenesis remain limited. We present an in vitro platform for lens morphogenesis by combining spatially patterned self-formed ectodermal autonomous multizone (SEAM) differentiation of human induced pluripotent stem cells (hiPSCs), with a lens optimised medium (LOM). Lentoids exhibited zone-specific organisation, upregulation of lens crystallins and connexins, and spatial protein localisation reflective of lens epithelial and fiber cells. LOM-treated cultures exhibited enhanced γ-crystallin expression, cadherin-mediated organisation, and capsule basement membrane deposition, alongside ultrastructural features of a maturing lens, including elongated cortical-like fibers, epithelial layering, and intercellular junctions with ball-and-socket-like interdigitations. Lentoids demonstrated self-renewing, preplacodal and presumptive lens ectodermal PAX6⁺/SIX3⁺/SOX2⁺ epithelial-like populations, which formed secondary lentoids, following activation of lens crystallin differentiation transcription factors—PROX1 and SOX1. These findings advance hiPSC-derived lens models and reveal an epithelial plasticity—offering a platform for studying ectodermal pathways, regenerative biology, and cataractogenesis. Lens differentiation requires the highest translational output to generate lifelong structural proteins, alongside a superior protein quality control system, and hiPSC-derived platforms provide a human model to study the limits of cellular differentiation and protein homeostasis.

Acknowledgements

The authors thank Tomohiko Katayama, Yuki Kobayashi and Yuki Ishikawa for laboratory assistance at The University of Osaka. The work was supported by BBSRC Research Grant Project BB/P017843/1 and quality-related research funding from Research England awarded to Anglia Ruskin University. The funders played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript. In memory of Ann and Gerald Harrington.

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Authors and Affiliations

  1. Faculty of Health, Medicine and Social Care, Centre for Biomedicine and Health Innovation, Anglia Ruskin University, Chelmsford, UK

    Jodie Harrington & Barbara Pierscionek

  2. Department of Stem Cells and Applied Medicine, The University of Osaka Graduate School of Medicine, Suita, Osaka, Japan

    Jodie Harrington, Xiaoqin Li, Ryuhei Hayashi & Kohji Nishida

  3. Department of Ophthalmology, The University of Osaka Graduate School of Medicine, Suita, Osaka, Japan

    Jodie Harrington & Ryuhei Hayashi

  4. The School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK

    Jodie Harrington, Robert D. Young, Justyn W. Regini & Andrew J. Quantock

  5. Institute for Open and Transdisciplinary Research Initiatives, The University of Osaka, Suita, Japan

    Ryuhei Hayashi & Kohji Nishida

  6. Premium Research Institute for Human Metaverse Medicine (WPI-PRIMe), The University of Osaka, Suita, Japan

    Kohji Nishida

Authors

  1. Jodie Harrington
  2. Robert D. Young
  3. Xiaoqin Li
  4. Ryuhei Hayashi
  5. Justyn W. Regini
  6. Andrew J. Quantock
  7. Barbara Pierscionek
  8. Kohji Nishida

Corresponding author

Correspondence to Barbara Pierscionek.

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Competing interests

The authors declare no competing interests.

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Cite this article

Harrington, J., Young, R.D., Li, X. et al. Human iPSC-derived lens organoids recapitulate lens development and morphogenesis in vitro. npj Regen Med (2026). https://doi.org/10.1038/s41536-026-00514-6

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  • Received: 23 January 2026

  • Accepted: 21 September 2026

  • Published: 15 October 2026

  • DOI: https://doi.org/10.1038/s41536-026-00514-6

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