Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction
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 accommo...
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KeAi Communications Co., Ltd.
2025-03-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Tianhui Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6923408a17314049b2f201d129cf9a05 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-6923408a17314049b2f201d129cf9a052025-01-26T05:04:25ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-03-0145446458Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstructionTianhui Chen0Zhongxing Chen1Juan Du2Min Zhang3Zexu Chen4Qingyi Gao5Aodong Chen6Qinghao Meng7Yang Sun8Yan liu9Linghao Song10Xinyue Wang11Pranav Prakash Edavi12Chen Xu13Hongmei Zhang14Jinhai Huang15Yongxiang Jiang16Eye 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, ChinaEye 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, ChinaMultidisciplinary 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, ChinaEye 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, ChinaEye 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, ChinaEye 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, ChinaEye 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, ChinaEye 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, ChinaEye 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, ChinaEye 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, ChinaEye 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, ChinaEye 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, ChinaShanghai Medical College (SHMC), Fudan University, Shanghai, 200031, ChinaDepartment 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.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.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.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.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.http://www.sciencedirect.com/science/article/pii/S2452199X24005231Ectopia lentisZonular fiber reconstructionInduced pluripotent stem cellsBiomimetic scaffoldsIn situ regeneration |
| spellingShingle | 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 Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction Bioactive Materials Ectopia lentis Zonular fiber reconstruction Induced pluripotent stem cells Biomimetic scaffolds In situ regeneration |
| title | Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction |
| title_full | Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction |
| title_fullStr | Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction |
| title_full_unstemmed | Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction |
| title_short | Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction |
| title_sort | reprogramming of ipscs to npcec like cells by biomimetic scaffolds for zonular fiber reconstruction |
| topic | Ectopia lentis Zonular fiber reconstruction Induced pluripotent stem cells Biomimetic scaffolds In situ regeneration |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24005231 |
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