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Survival of an HLA-mismatched, bioengineered RPE implant in dry age-related macular degeneration.
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.
Afiliación
  • Kashani AH; Wilmer Eye Institute, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, MD 21087 USA.
  • Lebkowski JS; Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA.
  • Hinton DR; 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 Ca
  • Zhu D; Department of Pathology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, 7503, Los Angeles, CA 90033, USA.
  • Faynus MA; 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.
  • Chen S; Orange County Retina Medical Group, 1200 N. Tustin Avenue, Suite 140, Santa Ana, CA 92705, USA.
  • Rahhal FM; Retina-Vitreous Associates Medical Group, 9001 Wilshire Boulevard, Suite 301, Beverly Hills, CA 90211, USA.
  • Avery RL; California Retina Consultants, 525 E. Micheltorena Street, Santa Barbara, CA 93103, USA.
  • Salehi-Had H; Retina Associates of Southern California, 7777 Edinger Avenue, Suite 234, Huntington Beach, CA 92647, USA.
  • Chan C; Southern California Desert Retina Consultants, University Park, 36-949 Cook Street, Suite 101, Palm Desert, CA 92211, USA.
  • Palejwala N; Retinal Consultants of Arizona, 15401 North 29th Avenue, Phoenix, AZ 85053, USA.
  • Ingram A; Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA.
  • Dang W; Center for Biomedicine and Genetics, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
  • Lin CM; Center for Biomedicine and Genetics, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
  • Mitra D; 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.
  • Martinez-Camarillo JC; Wilmer Eye Institute, Johns Hopkins University, 600 N. Wolfe Street, Baltimore, MD 21087 USA.
  • Bailey J; 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.
  • Arnold C; 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.
  • Pennington BO; 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.
  • Rao N; 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.
  • Johnson LV; Regenerative Patch Technologies, 150 Gabarda Way, Portola Valley, CA 94028, USA.
  • Clegg DO; Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, Mail Code 5060, University of California, Santa Barbara, CA 93016, USA.
  • Humayun MS; 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 S
Stem Cell Reports ; 17(3): 448-458, 2022 03 08.
Article en En | MEDLINE | ID: mdl-35120620
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prótesis e Implantes / Atrofia Geográfica / Degeneración Macular Límite: Humans Idioma: En Revista: Stem Cell Reports Año: 2022 Tipo del documento: Article
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Prótesis e Implantes / Atrofia Geográfica / Degeneración Macular Límite: Humans Idioma: En Revista: Stem Cell Reports Año: 2022 Tipo del documento: Article