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建立体外脉络膜复合体系统以筛选血管反应。

Establishment of an in vitro choroid complex system for vascular response screening.

机构信息

Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.

Laboratory of Photobiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.

出版信息

Sci Rep. 2024 Jul 12;14(1):16129. doi: 10.1038/s41598-024-67069-8.

Abstract

The choroid, a vascularized tissue situated between the retina and the sclera, plays a crucial role in maintaining ocular homeostasis. Despite its significance, research on choroidal abnormalities and the establishment of effective in vitro models have been limited. In this study, we developed an in vitro choroid model through the co-culture of human induced pluripotent stem cells (hiPSC)-derived endothelial cells (ECs) and mouse choroidal fibroblasts (msCFs) with hiPSC-derived retinal pigment epithelial (RPE) cells via a permeable membrane. This model, inclusive of ECs, CFs, and RPE cells, exhibited similarities with in vivo choroidal vessels, as confirmed through immunohistochemistry of extracellular matrix markers and vascular-related markers, as well as choroid angiogenesis sprouting assay analysis. The effectiveness of our in vitro model was demonstrated in assessing vascular changes induced by drugs targeting vasoregulation. Our model offers a valuable tool for gaining insights into the pathological mechanisms underlying choroid development and the progression of choroidal vascular diseases.

摘要

脉络膜是一种位于视网膜和巩膜之间的血管化组织,在维持眼球内环境稳定方面起着至关重要的作用。尽管其意义重大,但对脉络膜异常的研究以及建立有效的体外模型一直受到限制。在这项研究中,我们通过在可渗透膜上共培养人诱导多能干细胞(hiPSC)衍生的内皮细胞(ECs)和小鼠脉络膜成纤维细胞(msCFs)与 hiPSC 衍生的视网膜色素上皮(RPE)细胞,开发了一种体外脉络膜模型。该模型包含 ECs、CFs 和 RPE 细胞,通过细胞外基质标志物和血管相关标志物的免疫组织化学以及脉络膜血管生成发芽分析,证实其与体内脉络膜血管具有相似性。我们的体外模型在评估针对血管调节的药物引起的血管变化方面具有有效性。该模型为深入了解脉络膜发育和脉络膜血管疾病进展的病理机制提供了有价值的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46fc/11245503/bf5df73a9777/41598_2024_67069_Fig1_HTML.jpg

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