Repair effects of thermosensitive hydrogels combined with iPSC-derived corneal endothelial cells on rabbit corneal endothelial dysfunction

IF 9.4 1区医学 Q1 ENGINEERING, BIOMEDICAL

Acta Biomaterialia Pub Date : 2025-01-01 DOI:10.1016/j.actbio.2024.11.021

Jinhua Chi , Shuo Wang , Ruibao Ju , Shanshan Li , Chenqi Liu , Mingyu Zou , Tianjiao Xu , Yanting Wang , Zhiwen Jiang , Chaozhong Yang , Baoqin Han

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引用次数: 0

Abstract

Considering the limitations of human corneal endothelial cell proliferation as well as the severe shortage of corneal donations, it is imperative to develop improved methods of corneal endothelial cell transplantation. The purpose of this study was to construct a modified corneal endothelial cell transplantation approach using thermosensitive hydrogels combined with induced pluripotent stem cells (iPSCs)-derived human corneal endothelial cells (hCECs). In this study, thermosensitive hydrogels hydroxypropyl chitin/carboxymethyl chitosan (HPCH/CMCS) were fabricated, and their hydrogels properties and biocompatibility were investigated. Our results demonstrated that HPCH/CMCS hydrogels exhibited superior transparency, appropriate mechanical properties and favorable biocompatibility. A two-step induction method of small molecule compounds was employed, by which iPSCs were differentiated into hCECs via neural crest cells (NCCs). Additionally, a rabbit corneal endothelial dysfunction model was established in vivo, aiming to evaluate the safety and effectiveness of the combined method. Slit lamp microscope results indicated that significant transparency improvement could be noted in HPCH/CMCS/hCECs group (P = 0.006), whereas the corneal transparency was not homogeneous in different areas. Moreover, histological examinations and immunofluorescence analysis revealed that HPCH/CMCS/hCECs group showed a higher density of corneal endothelial cells and positive expressions of related markers. This study may provide ideas and experimental basis for the combined application of hydrogels and iPSC-derived corneal endothelial cells for corneal endothelial dysfunction.

Statement of Significance

Corneal transplantation is the most effective treatment for corneal endothelial dysfunction, which is challenged by issues such as corneal donor shortages and immune rejection. In this study, we proposed a combined transplantation method of cells and hydrogels for corneal endothelial dysfunction. We modified the protocols to obtain corneal endothelial cells from iPSCs by a two-step induction method. Besides, thermosensitive hydrogels with satisfactory biocompatibility and degradability were fabricated as fixation and support carriers of iPSC-derived corneal endothelial cells for in vivo transplantation. Experimental results demonstrated that this method could locally repair corneal endothelial dysfunction in rabbits, with the repaired corneas expressing relevant markers. This study presented a preliminary attempt to combine hydrogels and cells for corneal endothelial dysfunction.

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热敏水凝胶与 iPSC 衍生角膜内皮细胞相结合对兔角膜内皮功能障碍的修复作用。

考虑到人类角膜内皮细胞增殖的局限性以及角膜捐献的严重短缺，开发改进的角膜内皮细胞移植方法势在必行。本研究的目的是利用热敏水凝胶结合诱导多能干细胞（iPSCs）衍生的人角膜内皮细胞（hCECs），构建一种改良的角膜内皮细胞移植方法。本研究制备了热敏性水凝胶羟丙基甲壳素/羧甲基壳聚糖（HPCH/CMCS），并对其水凝胶特性和生物相容性进行了研究。结果表明，HPCH/CMCS 水凝胶具有优异的透明度、适当的机械性能和良好的生物相容性。我们采用了小分子化合物两步诱导法，通过神经嵴细胞（NCC）将 iPSCs 分化成 hCECs。此外，研究人员还在体内建立了兔子角膜内皮功能障碍模型，旨在评估该组合方法的安全性和有效性。裂隙灯显微镜结果表明，HPCH/CMCS/hCECs 组的角膜透明度明显改善（P = 0.006），但不同区域的角膜透明度并不均匀。此外，组织学检查和免疫荧光分析表明，HPCH/CMCS/hCECs 组的角膜内皮细胞密度更高，相关标记物也呈阳性表达。本研究可为联合应用水凝胶和 iPSCs 衍生角膜内皮细胞治疗角膜内皮功能障碍提供思路和实验依据。意义声明：角膜移植是治疗角膜内皮功能障碍最有效的方法，但角膜移植面临角膜供体短缺和免疫排斥等问题的挑战。在这项研究中，我们提出了一种细胞和水凝胶联合移植治疗角膜内皮功能障碍的方法。我们修改了方案，通过两步诱导法从 iPSCs 获得角膜内皮细胞。此外，我们还制作了具有良好生物相容性和降解性的热敏水凝胶，作为 iPSCs 衍生角膜内皮细胞的固定和支持载体，用于体内移植。实验结果表明，该方法可局部修复兔子角膜内皮功能障碍，修复后的角膜可表达相关标记。这项研究为结合水凝胶和细胞治疗角膜内皮功能障碍做出了初步尝试。

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来源期刊

Acta Biomaterialia 工程技术-材料科学：生物材料

CiteScore

16.80

自引率

3.10%

发文量

776

审稿时长

30 days

期刊介绍： Acta Biomaterialia is a monthly peer-reviewed scientific journal published by Elsevier. The journal was established in January 2005. The editor-in-chief is W.R. Wagner (University of Pittsburgh). The journal covers research in biomaterials science, including the interrelationship of biomaterial structure and function from macroscale to nanoscale. Topical coverage includes biomedical and biocompatible materials.