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

Amir H. Kashani, Jane S. Lebkowski, David R. Hinton, Danhong Zhu, Mohamed A. Faynus, Sanford Chen, Firas M. Rahhal, Robert L. Avery, Hani Salehi-Had, Clement Chan, Neal Palejwala, April Ingram, Wei Dang, Chih Min Lin, Debbie Mitra, Juan Carlos Martinez-Camarillo, Jeff Bailey, Cassidy Arnold, Britney O. Pennington, Narsing RaoLincoln V. Johnson, Dennis O. Clegg, Mark S. Humayun

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)448-458
Number of pages11
JournalStem Cell Reports
Volume17
Issue number3
DOIs
StatePublished - Mar 8 2022

Keywords

  • allogeneic
  • clinical trial
  • geographic atrophy
  • histology
  • implant
  • macular degeneration
  • parylene
  • polarized
  • retinal pigmented epithelium
  • stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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