Pluripotent stem cell-derived retinal organoid/cells for retinal regeneration therapies: A review.

In recent decades, many researchers have attempted to restore vision via transplantation of retina/retinal cells in eyes with retinal degeneration. The advent of induced pluripotent stem cells (iPSC) and retinal organoid induction technologies has boosted research on retinal regeneration therapy. Although the recognition of functional integration of graft photoreceptor cells in the host retina from 2006 has been disputed a decade later by the newly evidenced phenomenon denoted as "material transfer," several reports support possible reconstruction of the host-graft network in the retinas of both end-stage degeneration and in progressing degeneration cases. Based on proof of concept (POC) studies in animal models, a clinical study was conducted in Kobe, Japan in 2020 and showed the feasibility of cell-based therapy using iPSC retinal organoid technology. Although the graft potency of human embryonic stem (ES)/iPS cell-derived retinal organoid/retinal cells has been suggested by previous studies, much is still unknown regarding host capability, that is, how long-standing human degenerating retinas are capable of rewiring with transplanted cells. This review summarizes past POC studies on photoreceptor replacement therapy and introduces some new challenges to maximize the possible efficacy in future human clinical studies of regenerative therapy.