Transitioning into GMP-Compliance: Alternative Methods for Producing Retinal Organoids for Transplantation.

Abstract

Three-dimensional retinal organoids derived from human induced pluripotent stem cells (hiPSCs) are gaining much attention as a possible source for cell transplantation to treat retinal degenerative conditions. However, the protocol for producing retinal organoids is time and labor intensive, involving a sequence of precise steps, and thus has yet to be successfully translated into a Good Manufacturing Practice (GMP)-compliant procedure. This review seeks to define the progress that has already been made in the pursuit of designing a GMP-compliant, streamlined, and automated protocol for retinal organoid production for optimal clinical success. The reviewed literature compares various approaches for cell culture automation, appropriate xeno-free conditions, and cell sources for iPSC line generation; yet, there are still important gaps for these three key considerations that remain to be addressed. Thus, the authors also discuss further potential strategies to successfully achieve GMP-compliant production of retinal organoids for eventual safe and efficient use in clinical trials.Translational RelevanceDesigning a GMP-compliant protocol for three-dimensional retinal organoid production is of urgent need in order to bring transplantation of hiPSC-derived retinal tissue and derived cells to clinical trials – and ultimately patient treatment – for retinal degenerative diseases.