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

Author:

Koçak Gamze12ORCID,Uyulgan Sude12ORCID,Polatlı Elifsu12ORCID,Sarı Vedat12ORCID,Kahveci Burak12ORCID,Bursali Ahmet1,Binokay Leman12ORCID,Reçber Tuba3ORCID,Nemutlu Emirhan3ORCID,Mardinoğlu Adil45,Karakülah Gökhan12ORCID,Utine Canan Aslı16ORCID,Güven Sinan127ORCID

Affiliation:

1. Izmir Biomedicine and Genome Center Izmir 35340 Türkiye

2. Izmir International Biomedicine and Genome Institute Dokuz Eylül University Izmir 35340 Türkiye

3. Department of Analytical Chemistry Faculty of Pharmacy Hacettepe University Sıhhiye Ankara 06100 Türkiye

4. Science for Life Laboratory KTH – Royal Institute of Technology Stockholm Sweden

5. Centre for Host‐Microbiome Interactions Faculty of Dentistry Oral & Craniofacial Sciences King's College London London SE1 9RT UK

6. Department of Ophthalmology Dokuz Eylül University Hospital Dokuz Eylül University Izmir 35340 Türkiye

7. Department of Medical Biology and Genetics Faculty of Medicine Dokuz Eylül University Izmir 35340 Türkiye

Abstract

AbstractOphthalmic 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.

Publisher

Wiley

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