Izmir Biomedicine and Genome Center, Izmir, 35340, Türkiye.
Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir, 35340, Türkiye.
Adv Biol (Weinh). 2024 May;8(5):e2400018. doi: 10.1002/adbi.202400018. Epub 2024 Apr 19.
Ophthalmic diseases affect many people, causing partial or total loss of vision and a reduced quality of life. The anterior segment of the eye accounts for nearly half of all visual impairment that can lead to blindness. Therefore, there is a growing demand for ocular research and regenerative medicine that specifically targets the anterior segment to improve vision quality. This study aims to generate a microfluidic platform for investigating the formation of the anterior segment of the eye derived from human induced pluripotent stem cells (hiPSC) under various spatial-mechanoresponsive conditions. Microfluidic platforms are developed to examine the effects of dynamic conditions on the generation of hiPSCs-derived ocular organoids. The differentiation protocol is validated, and mechanoresponsive genes are identified through transcriptomic analysis. Several culture strategies is implemented for the anterior segment of eye cells in a microfluidic chip. hiPSC-derived cells showed anterior eye cell characteristics in mRNA and protein expression levels under dynamic culture conditions. The expression levels of yes-associated protein and transcriptional coactivator PDZ binding motif (YAP/TAZ) and PIEZO1, varied depending on the differentiation and growth conditions of the cells, as well as the metabolomic profiles under dynamic culture conditions.
眼科疾病影响众多人群，导致部分或全部视力丧失和生活质量下降。眼睛前段占所有可能导致失明的视力损害的近一半。因此，人们对眼部研究和再生医学的需求不断增长，这些研究专门针对前段以提高视力质量。本研究旨在生成一个微流控平台，用于在各种空间机械响应条件下研究源自人诱导多能干细胞（hiPSC）的眼睛前段的形成。微流控平台用于研究动态条件对 hiPSC 衍生类器官形成的影响。通过转录组分析验证了分化方案，并确定了机械响应基因。在微流控芯片中实施了几种用于眼睛前段细胞的培养策略。在动态培养条件下，hiPSC 衍生细胞在 mRNA 和蛋白表达水平上表现出前眼细胞特征。YAP/TAZ 和 PIEZO1 的表达水平取决于细胞的分化和生长条件以及动态培养条件下的代谢组学特征。
