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Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs.
Sharma, Ruchi; Khristov, Vladimir; Rising, Aaron; Jha, Balendu Shekhar; Dejene, Roba; Hotaling, Nathan; Li, Yichao; Stoddard, Jonathan; Stankewicz, Casey; Wan, Qin; Zhang, Connie; Campos, Mercedes Maria; Miyagishima, Kiyoharu J; McGaughey, David; Villasmil, Rafael; Mattapallil, Mary; Stanzel, Boris; Qian, Haohua; Wong, Wai; Chase, Lucas; Charles, Steve; McGill, Trevor; Miller, Sheldon; Maminishkis, Arvydas; Amaral, Juan; Bharti, Kapil.
Afiliação
  • Sharma R; Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Khristov V; Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Rising A; Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Jha BS; Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Dejene R; Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Hotaling N; Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Li Y; Visual Function Core, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Stoddard J; Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Stankewicz C; Cellular Dynamics International Inc. (a FUJIFILM company), Madison, WI 53711, USA.
  • Wan Q; Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Zhang C; Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Campos MM; Histology Core, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Miyagishima KJ; Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • McGaughey D; Ophthalmic Genetics and Visual Functional Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Villasmil R; Flow Cytometry Core, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Mattapallil M; Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Stanzel B; Macula Center Saar, Sulzbach Knappschaft Eye Clinic, Sulzbach/Saar 66280, Germany.
  • Qian H; Visual Function Core, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Wong W; Unit on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Chase L; Cellular Dynamics International Inc. (a FUJIFILM company), Madison, WI 53711, USA.
  • Charles S; Charles Retina Institute, Germantown, TN 38138, USA.
  • McGill T; Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.
  • Miller S; Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Maminishkis A; Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Amaral J; Office of Scientific Director, National Eye Institute, NIH, Bethesda, MD 20892, USA.
  • Bharti K; Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA. Kapilbharti@nei.nih.gov.
Sci Transl Med ; 11(475)2019 01 16.
Article em En | MEDLINE | ID: mdl-30651323
ABSTRACT
Considerable progress has been made in testing stem cell-derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Degeneração Retiniana / Células-Tronco / Epitélio Pigmentado da Retina Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Degeneração Retiniana / Células-Tronco / Epitélio Pigmentado da Retina Idioma: En Ano de publicação: 2019 Tipo de documento: Article