Generation of Anterior Segment of the Eye Cells from hiPSCs in Microfluidic Platforms

Adv Biol (Weinh). 2024 May;8(5):e2400018. doi: 10.1002/adbi.202400018. Epub 2024 Apr 19.

Abstract

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.

Keywords: hiPSC; mechanotransduction; metabolomics; ocular cell; on‐chip system; organoid; transcriptomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anterior Eye Segment / cytology
  • Anterior Eye Segment / metabolism
  • Cell Differentiation*
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Ion Channels / genetics
  • Ion Channels / metabolism
  • Lab-On-A-Chip Devices
  • Microfluidics / instrumentation
  • Microfluidics / methods
  • Organoids / cytology
  • Organoids / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins / metabolism

Substances

  • YAP-Signaling Proteins
  • PIEZO1 protein, human
  • Transcription Factors
  • Ion Channels
  • YAP1 protein, human