Retinal Pigment Epithelium Replacement Therapy for Age-Related Macular Degeneration: Are We There Yet?

Abstract

Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published clinical and preclinical studies have tested PSC-derived RPE as a potential treatment for AMD. Multiple approaches have been used to manufacture RPE cells, to validate them functionally, to confirm their safety profile, and to deliver them to patients either as suspension or as a monolayer patch. Since most of these studies are at an early regulatory approval stage, the primary outcome has been to determine the safety of RPE transplants in patients. However, preliminary signs of efficacy were observed in a few patients. Here, we review the current progress in the PSC-derived RPE transplantation field and provide a comparative assessment of various approaches under development as potential therapeutics for AMD.

Exosomes derived from neural progenitor cells preserve photoreceptors during retinal degeneration by inactivating microglia

“…The mNPC‐exo group had higher amplitudes of both a‐wave and b‐wave than that of the vehicle and the untreated groups at days 7 and 14, indicating the visual‐protective effects of mNPC‐exos, which was consistent with the anti‐apoptosis results in Figure 1(h). It was reported that even the vehicle injection, as a sham surgical intervention, could provide a photoreceptor protective effect in a limited time [44–46]. And this might be the reason that the ONL of vehicle groups had less apoptosis cells compared to the untreated groups at days 7 and 14 post‐injection in our study (Figure 1(h)).…”

Regulatory considerations for developing a phase I investigational new drug application for autologous induced pluripotent stem cells-based therapy product

“…Autologous iPSC‐derived product manufacturing can often extend from weeks to months 8,32 . The long manufacturing process increases risks of contamination and conflicts with the surgery schedule.…”

“…Furthermore, for an autologous manufacturing process, if multiple iPSC clones are simultaneously manufactured, cryopreservation allows the selection of clones that meet quality control (QC) criteria. Some potential stages for cryopreservation of intermediate products include (a) donor cells; (b) early passage iPSCs; (c) iPSCs at the passage before differentiation starts; and (d) progenitor and/or immature cells during differentiation 8 . It is important to note that these intermediate cryopreservation stages should be planned before pivotal preclinical IND‐enabling studies are conducted.…”

“…Replacement cell therapy, as the name suggests, aims to replace degenerated or diseased tissue with a new “healthier” tissue derived from pluripotent stem cells. Two types of pluripotent stem cells are in use for developing replacement cell therapies—embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) 8,10‐13 . Even though iPSCs were discovered almost a decade after ESCs, currently, iPSC use is gaining traction for developing cell‐based therapies.…”

“…Cell‐based therapies are quickly becoming mainstream treatment modalities, thanks to recent successes with cancer immunotherapies in the U.S. and mesenchymal stem cell‐based therapies in Europe 1‐7 . Advances in protocols to efficiently differentiate pluripotent stem cells into various cell types have opened the possibility of developing a new class of cell‐based therapies—the replacement cell therapy 8,9 . Replacement cell therapy, as the name suggests, aims to replace degenerated or diseased tissue with a new “healthier” tissue derived from pluripotent stem cells.…”