Effects of ECM Protein-coated Surfaces on the Generation of Retinal Pigment Epithelium Cells Differentiated from Human Pluripotent Stem Cells

Overview

Journal Regen Biomater

Specialty Biomedical Engineering

Date 2024 Sep 5

PMID 39233867

Authors

Zeyu Tian

Qian Liu

Hui-Yu Lin

Yu-Ru Zhu

Ling Ling

Tzu-Cheng Sung

Ting Wang

Wanqi Li

Min Gao

Sitian Cheng

Remya Rajan Renuka

Suresh Kumar Subbiah

Guoping Fan

Gwo-Jang Wu

Akon Higuchi

Affiliations

Soon will be listed here.

Abstract

Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.

Citing Articles

Material surface conjugated with fibroblast growth factor-2 for pluripotent stem cell culture and differentiation.

Sung T, Pan Z, Wang T, Lin H, Chang C, Hung L Regen Biomater. 2025; 12:rbaf003.

PMID: 39967781 PMC: 11835233. DOI: 10.1093/rb/rbaf003.

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