PMID- 35120620
OWN - NLM
STAT- MEDLINE
DCOM- 20220502
LR  - 20220716
IS  - 2213-6711 (Electronic)
IS  - 2213-6711 (Linking)
VI  - 17
IP  - 3
DP  - 2022 Mar 8
TI  - Survival of an HLA-mismatched, bioengineered RPE implant in dry age-related 
      macular degeneration.
PG  - 448-458
LID - S2213-6711(22)00045-5 [pii]
LID - 10.1016/j.stemcr.2022.01.001 [doi]
AB  - 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.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Kashani, Amir H
AU  - Kashani AH
AD  - Wilmer Eye Institute, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, 
      MD 21087 USA.
FAU - Lebkowski, Jane S
AU  - Lebkowski JS
AD  - Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA.
FAU - Hinton, David R
AU  - Hinton DR
AD  - Department of Pathology, Keck School of Medicine, University of Southern 
      California, 1441 Eastlake Avenue, 7503, Los Angeles, CA 90033, USA; USC Roski Eye 
      Institute, USC Ginsburg Institute for Biomedical Therapeutics and Department of 
      Ophthalmology, Keck School of Medicine, University of Southern California, 1450 
      San Pablo, Los Angeles, CA 90033, USA.
FAU - Zhu, Danhong
AU  - Zhu D
AD  - Department of Pathology, Keck School of Medicine, University of Southern 
      California, 1441 Eastlake Avenue, 7503, Los Angeles, CA 90033, USA.
FAU - Faynus, Mohamed A
AU  - Faynus MA
AD  - Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA; 
      Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      Mail Code 5060, University of California, Santa Barbara, CA 93016, USA.
FAU - Chen, Sanford
AU  - Chen S
AD  - Orange County Retina Medical Group, 1200 N. Tustin Avenue, Suite 140, Santa Ana, 
      CA 92705, USA.
FAU - Rahhal, Firas M
AU  - Rahhal FM
AD  - Retina-Vitreous Associates Medical Group, 9001 Wilshire Boulevard, Suite 301, 
      Beverly Hills, CA 90211, USA.
FAU - Avery, Robert L
AU  - Avery RL
AD  - California Retina Consultants, 525 E. Micheltorena Street, Santa Barbara, CA 
      93103, USA.
FAU - Salehi-Had, Hani
AU  - Salehi-Had H
AD  - Retina Associates of Southern California, 7777 Edinger Avenue, Suite 234, 
      Huntington Beach, CA 92647, USA.
FAU - Chan, Clement
AU  - Chan C
AD  - Southern California Desert Retina Consultants, University Park, 36-949 Cook 
      Street, Suite 101, Palm Desert, CA 92211, USA.
FAU - Palejwala, Neal
AU  - Palejwala N
AD  - Retinal Consultants of Arizona, 15401 North 29th Avenue, Phoenix, AZ 85053, USA.
FAU - Ingram, April
AU  - Ingram A
AD  - Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA.
FAU - Dang, Wei
AU  - Dang W
AD  - Center for Biomedicine and Genetics, Beckman Research Institute of City of Hope, 
      1500 East Duarte Road, Duarte, CA 91010, USA.
FAU - Lin, Chih-Min
AU  - Lin CM
AD  - Center for Biomedicine and Genetics, Beckman Research Institute of City of Hope, 
      1500 East Duarte Road, Duarte, CA 91010, USA.
FAU - Mitra, Debbie
AU  - Mitra D
AD  - USC Roski Eye Institute, USC Ginsburg Institute for Biomedical Therapeutics and 
      Department of Ophthalmology, Keck School of Medicine, University of Southern 
      California, 1450 San Pablo, Los Angeles, CA 90033, USA.
FAU - Martinez-Camarillo, Juan Carlos
AU  - Martinez-Camarillo JC
AD  - Wilmer Eye Institute, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, 
      MD 21087 USA.
FAU - Bailey, Jeff
AU  - Bailey J
AD  - Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA; 
      Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      Mail Code 5060, University of California, Santa Barbara, CA 93016, USA.
FAU - Arnold, Cassidy
AU  - Arnold C
AD  - Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA; 
      Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      Mail Code 5060, University of California, Santa Barbara, CA 93016, USA.
FAU - Pennington, Britney O
AU  - Pennington BO
AD  - Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA; 
      Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      Mail Code 5060, University of California, Santa Barbara, CA 93016, USA.
FAU - Rao, Narsing
AU  - Rao N
AD  - USC Roski Eye Institute, USC Ginsburg Institute for Biomedical Therapeutics and 
      Department of Ophthalmology, Keck School of Medicine, University of Southern 
      California, 1450 San Pablo, Los Angeles, CA 90033, USA.
FAU - Johnson, Lincoln V
AU  - Johnson LV
AD  - Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA.
FAU - Clegg, Dennis O
AU  - Clegg DO
AD  - Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, 
      Mail Code 5060, University of California, Santa Barbara, CA 93016, USA.
FAU - Humayun, Mark S
AU  - Humayun MS
AD  - USC Roski Eye Institute, USC Ginsburg Institute for Biomedical Therapeutics and 
      Department of Ophthalmology, Keck School of Medicine, University of Southern 
      California, 1450 San Pablo, Los Angeles, CA 90033, USA; Department of Biomedical 
      Engineering, Denney Research Center (DRB) 140, University of Southern California, 
      1042 Downey Way, Los Angeles, CA 90089, USA. Electronic address: humayun@usc.edu.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220203
PL  - United States
TA  - Stem Cell Reports
JT  - Stem cell reports
JID - 101611300
SB  - IM
MH  - *Geographic Atrophy/therapy
MH  - Human Embryonic Stem Cells/pathology
MH  - Humans
MH  - *Macular Degeneration/pathology/therapy
MH  - *Prostheses and Implants/adverse effects
MH  - Retinal Pigment Epithelium/pathology
PMC - PMC9039755
OTO - NOTNLM
OT  - allogeneic
OT  - clinical trial
OT  - geographic atrophy
OT  - histology
OT  - implant
OT  - macular degeneration
OT  - parylene
OT  - polarized
OT  - retinal pigmented epithelium
OT  - stem cells
EDAT- 2022/02/06 06:00
MHDA- 2022/05/03 06:00
PMCR- 2022/02/03
CRDT- 2022/02/05 05:33
PHST- 2021/02/02 00:00 [received]
PHST- 2022/01/03 00:00 [revised]
PHST- 2022/01/04 00:00 [accepted]
PHST- 2022/02/06 06:00 [pubmed]
PHST- 2022/05/03 06:00 [medline]
PHST- 2022/02/05 05:33 [entrez]
PHST- 2022/02/03 00:00 [pmc-release]
AID - S2213-6711(22)00045-5 [pii]
AID - 10.1016/j.stemcr.2022.01.001 [doi]
PST - ppublish
SO  - Stem Cell Reports. 2022 Mar 8;17(3):448-458. doi: 10.1016/j.stemcr.2022.01.001. 
      Epub 2022 Feb 3.