Submacular hESC-RPE Transplant in Macaques

Article: Developing a treatment for vision loss through transplant of photoreceptor precursors
Source: National University of Singapore, School of Medicine (Singapore)
Published: October 18, 2021

Inherited retinal diseases (IRD) are estimated to affect 1 in 2000 people globally. However, the extent of heterogeneity in inherited retinal diseases, involving more than 260 identified genes, limits the widespread application of gene therapy, which is often specific to singular or related genes. Gene thereapy also has limited success in advanced stages of retinal degeneration, wherein significant photoreceptor death has already occurred. The advent of stem cell therapy, such as induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) therapy, provides an alternative route to treatment of retinal diseases through regenerative medicine, independent of the underlying genetics. There has been some success in visual improvement in smaller animal models following transplantation of retinal photoreceptor precursors, although the results are more limited in larger mammals. Researchers in Singapore are exploring the therapeutic potential of photoreceptor precursors derived from human embryonic stem cell (hESC)-derived RPE on a scaffold. The most recent experiments in 11 cynomolgus monkeys (macaques) showed "both structural and functional submacular integrations of hESC-RPE xenografts." In particular, microscope-integrated intraoperative (miOCT) typically revealed foveal disruption (trapped residual subretinal fluid), a negative outcome. However, electroretinogram (ERG) showed amplitude and peak time preservation in cases with favorable surgical outcomes, and histology confirmed photoreceptor preservation above the grafts and in vivo phagocytosis by hESC-RPE, i.e., active RPE function. Finally, the immunosuppression protocol was effective at suppressing retinal T cells and microglia. This is all to say that research in stem cell therapy for IRDs is still in progress. However, the researchers anticipate that refinements in technique will bring improvements to this area of therapy.

Post-operative in vivo analysis of the xenografts with multimodal imaging

My rating of this study: ⭐⭐

Liu Z, Ilmarinen T, Tan GSW, et al. "Submacular integration of hESC-RPE monolayer xenografts in a surgical non-human primate model." Stem Cell Research & Therapy.  12:423. 27 July 2021. https://doi.org/10.1186/s13287-021-02395-6