关键词: Choroid Endothelial cell Fibroblast In vitro culture system Vasoregulation

Mesh : Choroid / blood supply metabolism Animals Humans Mice Induced Pluripotent Stem Cells / cytology metabolism Endothelial Cells / metabolism Retinal Pigment Epithelium / metabolism cytology Coculture Techniques Fibroblasts / metabolism Choroidal Neovascularization / metabolism pathology Cells, Cultured

来  源:   DOI:10.1038/s41598-024-67069-8   PDF(Pubmed)

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,位于视网膜和巩膜之间的血管化组织,在维持眼稳态中起着至关重要的作用。尽管意义重大,脉络膜异常的研究和有效体外模型的建立一直受到限制。在这项研究中,我们通过人诱导多能干细胞(hiPSC)来源的内皮细胞(ECs)和小鼠脉络膜成纤维细胞(msCFs)与hiPSC来源的视网膜色素上皮(RPE)细胞的共培养,建立了体外脉络膜模型。这个模型,包括EC在内,CFs,和RPE细胞,表现出与体内脉络膜血管的相似性,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证实,以及脉络膜血管生成发芽测定分析。我们的体外模型在评估由靶向血管调节的药物诱导的血管变化方面的有效性得到了证明。我们的模型为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。
公众号