Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs
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...
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| Published in | Science translational medicine Vol. 11; no. 475 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
16.01.2019
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| Subjects | |
| Online Access | Get more information |
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| 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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| AbstractList | 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. |
| Author | Amaral, Juan McGill, Trevor Dejene, Roba Campos, Mercedes Maria Wan, Qin Miller, Sheldon Maminishkis, Arvydas Mattapallil, Mary Stanzel, Boris Villasmil, Rafael Rising, Aaron Charles, Steve Jha, Balendu Shekhar Khristov, Vladimir Chase, Lucas Wong, Wai Sharma, Ruchi Stankewicz, Casey Zhang, Connie McGaughey, David Hotaling, Nathan Miyagishima, Kiyoharu J Bharti, Kapil Qian, Haohua Li, Yichao Stoddard, Jonathan |
| Author_xml | – sequence: 1 givenname: Ruchi orcidid: 0000-0002-2138-6462 surname: Sharma fullname: Sharma, Ruchi organization: Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 2 givenname: Vladimir orcidid: 0000-0002-7778-3993 surname: Khristov fullname: Khristov, Vladimir organization: Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 3 givenname: Aaron orcidid: 0000-0002-0725-9758 surname: Rising fullname: Rising, Aaron organization: Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 4 givenname: Balendu Shekhar orcidid: 0000-0002-6509-8171 surname: Jha fullname: Jha, Balendu Shekhar organization: Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 5 givenname: Roba surname: Dejene fullname: Dejene, Roba organization: Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 6 givenname: Nathan surname: Hotaling fullname: Hotaling, Nathan organization: Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 7 givenname: Yichao orcidid: 0000-0003-2697-2556 surname: Li fullname: Li, Yichao organization: Visual Function Core, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 8 givenname: Jonathan surname: Stoddard fullname: Stoddard, Jonathan organization: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA – sequence: 9 givenname: Casey surname: Stankewicz fullname: Stankewicz, Casey organization: Cellular Dynamics International Inc. (a FUJIFILM company), Madison, WI 53711, USA – sequence: 10 givenname: Qin surname: Wan fullname: Wan, Qin organization: Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 11 givenname: Connie surname: Zhang fullname: Zhang, Connie organization: Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 12 givenname: Mercedes Maria orcidid: 0000-0003-1331-1484 surname: Campos fullname: Campos, Mercedes Maria organization: Histology Core, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 13 givenname: Kiyoharu J surname: Miyagishima fullname: Miyagishima, Kiyoharu J organization: Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 14 givenname: David orcidid: 0000-0002-9224-2888 surname: McGaughey fullname: McGaughey, David organization: Ophthalmic Genetics and Visual Functional Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 15 givenname: Rafael orcidid: 0000-0002-8956-2979 surname: Villasmil fullname: Villasmil, Rafael organization: Flow Cytometry Core, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 16 givenname: Mary surname: Mattapallil fullname: Mattapallil, Mary organization: Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 17 givenname: Boris surname: Stanzel fullname: Stanzel, Boris organization: Macula Center Saar, Sulzbach Knappschaft Eye Clinic, Sulzbach/Saar 66280, Germany – sequence: 18 givenname: Haohua orcidid: 0000-0002-1114-4697 surname: Qian fullname: Qian, Haohua organization: Visual Function Core, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 19 givenname: Wai orcidid: 0000-0003-0681-4016 surname: Wong fullname: Wong, Wai organization: Unit on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 20 givenname: Lucas surname: Chase fullname: Chase, Lucas organization: Cellular Dynamics International Inc. (a FUJIFILM company), Madison, WI 53711, USA – sequence: 21 givenname: Steve surname: Charles fullname: Charles, Steve organization: Charles Retina Institute, Germantown, TN 38138, USA – sequence: 22 givenname: Trevor surname: McGill fullname: McGill, Trevor organization: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA – sequence: 23 givenname: Sheldon orcidid: 0000-0001-7495-2547 surname: Miller fullname: Miller, Sheldon organization: Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 24 givenname: Arvydas orcidid: 0000-0003-3345-3375 surname: Maminishkis fullname: Maminishkis, Arvydas organization: Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 25 givenname: Juan orcidid: 0000-0001-8755-9170 surname: Amaral fullname: Amaral, Juan organization: Office of Scientific Director, National Eye Institute, NIH, Bethesda, MD 20892, USA – sequence: 26 givenname: Kapil orcidid: 0000-0003-4884-3173 surname: Bharti fullname: Bharti, Kapil email: Kapilbharti@nei.nih.gov organization: Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA. Kapilbharti@nei.nih.gov |
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| Title | Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs |
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