Efficient generation of human retinal pigment epithelium cells via chemically induced pluripotency

The eye is an ideal target organ for Human induced pluripotent stem cells (hiPSCs)-based cellular therapies. However, the application of hiPSCs in ocular disease treatment is still challenging because the production of clinical-grade autologous hiPSCs via genetic techniques remains expensive, time-consuming, and subject to safety concerns. Addressing these challenges, our study utilized a recently reported chemical method to derive human chemically induced pluripotent stem cells (hCiPSCs), which simplified the reprogramming process by using small molecules, offering a more straightforward and potentially safer alternative to derive hiPSCs. Moreover, we demonstrate that hCiPSCs can be efficiently differentiated into functional retinal pigment epithelium (RPE) cells, showing promise for the treatment of age-related macular degeneration (AMD) and other retinal diseases. Our study provides a method for the efficient and safe production of autologous retinal cells, facilitating the advancement of personalized stem cell therapies for ocular diseases. To reprogram the human adult adipose tissue-derived stromal cells (hADSCs) into human chemically induced pluripotent stem cells (hCiPSCs), and differentiate the latter into retinal pigment epithelial (RPE) cells. We analyzed the transcriptomic data of hCiPSCs, hADSCs, and human embryonic stem cells to verify the pluripotency of hCiPSCs. We further analyzed the transcriptome differences among hCiPSCs-RPE, hCiPSCs and human primary RPE reported in GEO database (GSE210331).