Retinal Photoreceptor Differentiation from Human Pluripotent Stem Cells for 3-D Bio-Printing

Retinal cells including light sensing photoreceptors lack regeneration potential leading to permanent vision loss. Various approaches including gene therapy, cell transplantation, and optogenetics are being studied to treat or restore the irreversible damage. Generating retinal photoreceptors using human pluripotent stem cells (iPSCs) holds great potential in treating as well developing in vitro models for better understanding and screening of various formulations for retinal degenerative diseases like retinitis and age-related macular degeneration. In this study, human iPSC line (iPSK3 cells) derived from skin fibroblasts cells was differentiated into retinal photoreceptors following a small molecule-based retinal induction protocol. We observed that retinal photoreceptors differentiated from the iPSCs showed marker expression for retinal progenitor cells (LHX2), ganglionic cells (PAX6), pan-photoreceptors (OTX2, CRX), and differentiated ganglionic cells (BRN3). In order to mimic the native environment during retinal development, we are optimizing suitable bio-inks in order to 3D bio-print the retinal progenitors and photoreceptors. This study provides evidence for recapitulation of the native retinal environment as well as development of photoreceptor models for drug screening purposes.

Reference

Jie Zhu, Joseph Reynolds, Thelma Garcia, Helen Cifuentes, et.al, Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line, Stem Cells Translational Medicine, 2018;7:210-219.