Survival of an HLA-mismatched, bioengineered RPE implant in dry age-related macular degeneration.

TitleSurvival of an HLA-mismatched, bioengineered RPE implant in dry age-related macular degeneration.
Publication TypeJournal Article
Year of Publication2022
AuthorsKashani AH, Lebkowski JS, Hinton DR, Zhu D, Faynus MA, Chen S, Rahhal FM, Avery RL, Salehi-Had H, Chan C, Palejwala N, Ingram A, Dang W, Lin C-M, Mitra D, Martinez-Camarillo JCarlos, Bailey J, Arnold C, Pennington BO, Rao N, Johnson LV, Clegg DO, Humayun MS
JournalStem Cell Reports
Date Published2022 03 08
KeywordsGeographic Atrophy, Human Embryonic Stem Cells, Humans, Macular Degeneration, Prostheses and Implants, Retinal Pigment Epithelium

Cell-based therapies face challenges, including poor cell survival, immune rejection, and integration into pathologic tissue. We conducted an open-label phase 1/2a clinical trial to assess the safety and preliminary efficacy of a subretinal implant consisting of a polarized monolayer of allogeneic human embryonic stem cell-derived retinal pigmented epithelium (RPE) cells in subjects with geographic atrophy (GA) secondary to dry age-related macular degeneration. Postmortem histology from one subject with very advanced disease shows the presence of donor RPE cells 2 years after implantation by immunoreactivity for RPE65 and donor-specific human leukocyte antigen (HLA) class I molecules. Markers of RPE cell polarity and phagocytosis suggest donor RPE function. Further histologic examination demonstrated CD34 structures beneath the implant and CD4, CD68, and FoxP3 cells in the tissue. Despite significant donor-host HLA mismatch, no clinical signs of retinitis, vitreitis, vasculitis, choroiditis, or serologic immune response were detected in the deceased subject or any other subject in the study. Subretinally implanted, HLA-mismatched donor RPE cells survive, express functional markers, and do not elicit clinically detectable intraocular inflammation or serologic immune responses even without long-term immunosuppression.

Alternate JournalStem Cell Reports
PubMed ID35120620
PubMed Central IDPMC9039755