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体外人角膜器官培养模型中的组织工程化角膜内皮移植

Tissue engineered corneal endothelium transplantation in an ex vivo human cornea organ culture model.

作者信息

Tsai Meng-Chen, Kureshi Alvena, Daniels Julie T

机构信息

UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.

Centre for 3D Models of Health and Disease, Division of Surgery and Interventional Science, University College London, London, UK.

出版信息

Sci Rep. 2025 Apr 12;15(1):12571. doi: 10.1038/s41598-025-96494-6.

Abstract

Transplantation of corneal tissue is the standard treatment for irreversible corneal endothelium decompensation by replacing the malfunctioning corneal endothelial cells and Descemet's membrane. However, this surgery depends on limited donor tissue supply. Thus, developing suitable alternatives for donor grafting material through a tissue engineering approach is needed to enable the transplantation of cultured endothelial cells to restore normal endothelial function. Here, we proposed using a plastic compressed collagen 3D matrix called Real Architecture For 3D Tissues (RAFT) as a scaffold for cell culture. The porcine cornea endothelial cells (PCECs) were seeded on RAFT to construct a tissue-engineered corneal endothelium. Then, the porcine cell-seeded-RAFT graft was transplanted onto a human cornea and maintained in an ex vivo organ culture model. The results showed that PCECs formed a high-density monolayer on RAFT expressing endothelial cell markers, ZO-1, Na/K ATPase and N-cadherin. More importantly, the cell-seeded RAFT transplantation successfully restored corneal endothelium function, drawing the thickness of endothelium-wounded cornea back to normal in two weeks of the ex vivo human cornea organ culture.

摘要

角膜组织移植是通过替换功能失调的角膜内皮细胞和Descemet膜来治疗不可逆角膜内皮失代偿的标准方法。然而,这种手术依赖于有限的供体组织供应。因此,需要通过组织工程方法开发合适的供体移植材料替代品,以使培养的内皮细胞能够移植,恢复正常的内皮功能。在此,我们提出使用一种名为3D组织真实架构(RAFT)的塑料压缩胶原蛋白3D基质作为细胞培养支架。将猪角膜内皮细胞(PCECs)接种在RAFT上构建组织工程化角膜内皮。然后,将接种有猪细胞的RAFT移植物移植到人类角膜上,并在体外器官培养模型中进行维持。结果表明,PCECs在表达内皮细胞标志物ZO-1、钠钾ATP酶和N-钙黏蛋白的RAFT上形成了高密度单层。更重要的是,接种细胞的RAFT移植成功恢复了角膜内皮功能,在体外人类角膜器官培养两周后,使内皮受损角膜的厚度恢复正常。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c854/11993598/a74448d149e4/41598_2025_96494_Fig1_HTML.jpg

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