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

• Published in: Stem cell reports Vol. 17; no. 3; pp. 448 - 458
• Main Authors: Kashani, Amir H., Lebkowski, Jane S., Hinton, David R., Zhu, Danhong, Faynus, Mohamed A., Chen, Sanford, Rahhal, Firas M., Avery, Robert L., Salehi-Had, Hani, Chan, Clement, Palejwala, Neal, Ingram, April, Dang, Wei, Lin, Chih-Min, Mitra, Debbie, Martinez-Camarillo, Juan Carlos, Bailey, Jeff, Arnold, Cassidy, Pennington, Britney O., Rao, Narsing, Johnson, Lincoln V., Clegg, Dennis O., Humayun, Mark S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.03.2022; Elsevier
• Subjects: allogeneic; clinical trial; geographic atrophy; Geographic Atrophy - therapy; histology; Human Embryonic Stem Cells - pathology; Humans; implant; macular degeneration; Macular Degeneration - pathology; Macular Degeneration - therapy; parylene; polarized; Prostheses and Implants - adverse effects; Retinal Pigment Epithelium - pathology; retinal pigmented epithelium; stem cells; clinical trial; stem cells; histology; geographic atrophy; allogeneic; implant; parylene; polarized; retinal pigmented epithelium; macular degeneration
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2022.01.001

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. •Clinical trial of allogeneic RPE cell transplant as AMD therapeutic•Postmortem histology shows 2-year survival and function of donor RPE cells•Transplanted RPE cells are mature, polarized, and phagocytic•Serologic immune and clinical cellular inflammatory responses are not detected In this article, Humayun and colleagues report the histologic assessment of a bioengineered RPE cell implant, called CPCB-RPE1, in a clinical trial for advanced dry age-related macular degeneration. The data show that highly HLA-mismatched allogeneic stem cell-derived RPE cells implanted subretinally survive and maintain a mature phenotype in the subretinal space for >2 years.