Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction

Tianhui Chen; Zhongxing Chen; Juan Du; Min Zhang; Zexu Chen; Qingyi Gao; Aodong Chen; Qinghao Meng; Yang Sun; Yan liu; Linghao Song; Xinyue Wang; Pranav Prakash Edavi; Chen Xu; Hongmei Zhang; Jinhai Huang; Yongxiang Jiang

Bioactive Materials (Mar 2025)

Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction

Tianhui Chen,
Zhongxing Chen,
Juan Du,
Min Zhang,
Zexu Chen,
Qingyi Gao,
Aodong Chen,
Qinghao Meng,
Yang Sun,
Yan liu,
Linghao Song,
Xinyue Wang,
Pranav Prakash Edavi,
Chen Xu,
Hongmei Zhang,
Jinhai Huang,
Yongxiang Jiang

Affiliations

Tianhui Chen: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Zhongxing Chen: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Juan Du: Multidisciplinary Centre for Advanced Materials, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai, 201620, China
Min Zhang: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Zexu Chen: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Qingyi Gao: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Aodong Chen: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Qinghao Meng: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Yang Sun: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Yan liu: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Linghao Song: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Xinyue Wang: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China
Pranav Prakash Edavi: Shanghai Medical College (SHMC), Fudan University, Shanghai, 200031, China
Chen Xu: Department of Physiology and Pathophysiology, Shanghai Key Laboratory of Bioactive Small Molecules, School of Basic Medical Sciences, Fudan University, 138 Xueyuan Road, Shanghai, 200032, China; Corresponding author.
Hongmei Zhang: School of Chemistry and Chemical Engineering, Shanghai Engineering Research Center of Pharmaceutical Intelligent Equipment, Shanghai University of Engineering Science, 333 Longteng Rd., Shanghai, 201620, China; Corresponding authors.
Jinhai Huang: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China; Corresponding authors. Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fenyang Rd, Shanghai, 200031, China.
Yongxiang Jiang: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China; Corresponding author. Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fenyang Rd, Shanghai, 200031, China.

Journal volume & issue: Vol. 45
pp. 446 – 458

Abstract

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Ectopia lentis (EL), characterised by impaired zonular fibers originating from non-pigmented ciliary epithelial cells (NPCEC), presents formidable surgical complexities and potential risks of visual impairment. Cataract surgery is the only treatment method for EL, but it leads to the loss of accommodative power of the lens post-operatively. Furthermore, the challenge of repairing zonular ligaments in situ remains a significant global issue. Ocular tissue and aqueous humour samples from patients with EL were subjected to RNA sequencing and Olink high-throughput proteomic analysis, revealing the downregulation of pathogenic genes (FBN1, MFAP2) and upregulation of secretory proteins (IL-12, MMP-1). The high expression of FBN1 and MFAP2 in NPCECs suggests their potential as candidates for zonular fiber construction; however, the limited availability of donor sources restricts the feasibility of NPCEC transplantation therapy. The reprogramming and directional differentiation of induced pluripotent stem cells (iPSC) to NPCEC was successfully achieved using the developed biomimetic scaffolds that mimic the microstructures of natural radial zonular fibers. Excitingly, the single injection of induced NPCEC-like cells significantly contributed to restoring and enhancing mechanical properties in zonular fiber structures in a rabbit model with EL. This proposed in situ iPSC-based regeneration technique might serve as an innovative therapeutic strategy for clinical EL patients, reduce the cataract surgery rate, and retain the adjustment capacity of inherent lentis.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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