Case Study: Assessment of CPCB-RPE1 Retinal Patch in a Postmortem Patient Two Years Post-Implantation

Article: Stem cell-derived retinal patch is shown to survive two years post-implantation
Source: University of California, Santa Barbara
Published: March 15, 2022

CPCB-RPE1 retinal patch in implanted eye 1 year post-op (upper right)

One area of research in the treatment of degenerative diseases of the retina, such as age-related macular degeneration (AMD), is through stem cells. These stem cells are delivered through subretinal injection or through the implantation of a patch of cells beneath the retina. Researchers at UCSB report a follow-up for the California Project to Cure Blindness – Retinal Pigment Epithelium 1 (CPCB-RPE1) patch, which has been in development since 2013 and consists of a monolayer of human stem cell-derived RPE cells cultured on an ultrathin membrane of biologically inert parylene. Early results of Phase 1 clinical trials were encouraging. Of the 15 patients in the initial cohort, four showed visual improvement and five experienced stabilization of their vision. More recently, one of the patients, named "Subject 125," passed away from pneumonia, allowing the researchers the opportunity to study her donated eyes postmortem and check the progress of their patch. Staining and immunoreactivity testing confirmed that the cells were donor RPE cells and that they were well-oriented in a polarized position (like in a natural retina). Furthermore, retinal histology revealed phagocytic activity, demonstrating that the RPE stem cells were functional in their role of recycling photoreceptor outer segment discs. Importantly, after two years, the presence of the patch did not trigger signs of rejection, such as inflammation, neovascularization, or scarring, even without immunosuppressants (which were stopped two months after implantation). The research team are working on Phase 2 of the clinical trials to test the patch's effectiveness, as well as developing advances to extend the patch's shelf life through cryopreservation and composite implants that combine multiple retinal cell types to treat various stages of retinal disease.

Retinal histopathology shows active RPE implant cells by presence of RPE65 (green) (B). Donor RPE cells express Na+/K+-ATPase (red) in a largely apical distribution consistent with mature and functional RPE (C). Donor RPE of the implant suggests presence of phagosomes containing photoreceptor outer segments; yellow immunofluorescence represents red-stained phagosomes (rhodopsin) in green-stained cytoplasm (RPE65) (G).

My rating of this study: ⭐⭐

Kashani AH, Lebkowski JS, Hinton DR, et al. "Survival of an HLA-mismatched, bioengineered RPE implant in dry age-related macular degeneration." Stem Cell Reports. 17(3):P448-458. 8 March 2022.
https://doi.org/10.1016/j.stemcr.2022.01.001