Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats
End-stage age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are two major retinal degenerative (RD) conditions that result in irreversible vision loss. Permanent eye damage can also occur in battlefields or due to accidents. This suggests there is an unmet need for developing effe...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.752958/full |
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| author | Biju B. Thomas Biju B. Thomas Bin Lin Bin Lin Juan Carlos Martinez-Camarillo Juan Carlos Martinez-Camarillo Danhong Zhu Danhong Zhu Bryce T. McLelland Bryce T. McLelland Gabriel Nistor Hans S. Keirstead Mark S. Humayun Mark S. Humayun Magdalene J. Seiler Magdalene J. Seiler Magdalene J. Seiler Magdalene J. Seiler |
| author_facet | Biju B. Thomas Biju B. Thomas Bin Lin Bin Lin Juan Carlos Martinez-Camarillo Juan Carlos Martinez-Camarillo Danhong Zhu Danhong Zhu Bryce T. McLelland Bryce T. McLelland Gabriel Nistor Hans S. Keirstead Mark S. Humayun Mark S. Humayun Magdalene J. Seiler Magdalene J. Seiler Magdalene J. Seiler Magdalene J. Seiler |
| author_sort | Biju B. Thomas |
| collection | DOAJ |
| description | End-stage age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are two major retinal degenerative (RD) conditions that result in irreversible vision loss. Permanent eye damage can also occur in battlefields or due to accidents. This suggests there is an unmet need for developing effective strategies for treating permanent retinal damages. In previous studies, co-grafted sheets of fetal retina with its retinal pigment epithelium (RPE) have demonstrated vision improvement in rat retinal disease models and in patients, but this has not yet been attempted with stem-cell derived tissue. Here we demonstrate a cellular therapy for irreversible retinal eye injuries using a “total retina patch” consisting of retinal photoreceptor progenitor sheets and healthy RPE cells on an artificial Bruch’s membrane (BM). For this, retina organoids (ROs) (cultured in suspension) and polarized RPE sheets (cultured on an ultrathin parylene substrate) were made into a co-graft using bio-adhesives [gelatin, growth factor-reduced matrigel, and medium viscosity (MVG) alginate]. In vivo transplantation experiments were conducted in immunodeficient Royal College of Surgeons (RCS) rats at advanced stages of retinal degeneration. Structural reconstruction of the severely damaged retina was observed based on histological assessments and optical coherence tomography (OCT) imaging. Visual functional assessments were conducted by optokinetic behavioral testing and superior colliculus electrophysiology. Long-term survival of the co-graft in the rat subretinal space and improvement in visual function were observed. Immunohistochemistry showed that co-grafts grew, generated new photoreceptors and developed neuronal processes that were integrated into the host retina. This novel approach can be considered as a new therapy for complete replacement of a degenerated retina. |
| first_indexed | 2024-12-13T22:25:01Z |
| format | Article |
| id | doaj.art-e376a8ebe9c5472c8dce364154ef862d |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-13T22:25:01Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-e376a8ebe9c5472c8dce364154ef862d2022-12-21T23:29:15ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-10-011510.3389/fnins.2021.752958752958Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons RatsBiju B. Thomas0Biju B. Thomas1Bin Lin2Bin Lin3Juan Carlos Martinez-Camarillo4Juan Carlos Martinez-Camarillo5Danhong Zhu6Danhong Zhu7Bryce T. McLelland8Bryce T. McLelland9Gabriel Nistor10Hans S. Keirstead11Mark S. Humayun12Mark S. Humayun13Magdalene J. Seiler14Magdalene J. Seiler15Magdalene J. Seiler16Magdalene J. Seiler17Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA, United StatesUSC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United StatesDepartment of Physical Medicine and Rehabilitation, University of California, Irvine, Irvine, CA, United StatesStem Cell Research Center, University of California, Irvine, Irvine, CA, United StatesDepartment of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA, United StatesUSC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United StatesDepartment of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA, United StatesDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Physical Medicine and Rehabilitation, University of California, Irvine, Irvine, CA, United StatesStem Cell Research Center, University of California, Irvine, Irvine, CA, United StatesAIVITA Biomedical Inc., Irvine, CA, United StatesAIVITA Biomedical Inc., Irvine, CA, United StatesDepartment of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA, United StatesUSC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United StatesDepartment of Physical Medicine and Rehabilitation, University of California, Irvine, Irvine, CA, United StatesStem Cell Research Center, University of California, Irvine, Irvine, CA, United StatesDepartment of Ophthalmology, University of California, Irvine, Irvine, CA, United StatesDepartment of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, United StatesEnd-stage age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are two major retinal degenerative (RD) conditions that result in irreversible vision loss. Permanent eye damage can also occur in battlefields or due to accidents. This suggests there is an unmet need for developing effective strategies for treating permanent retinal damages. In previous studies, co-grafted sheets of fetal retina with its retinal pigment epithelium (RPE) have demonstrated vision improvement in rat retinal disease models and in patients, but this has not yet been attempted with stem-cell derived tissue. Here we demonstrate a cellular therapy for irreversible retinal eye injuries using a “total retina patch” consisting of retinal photoreceptor progenitor sheets and healthy RPE cells on an artificial Bruch’s membrane (BM). For this, retina organoids (ROs) (cultured in suspension) and polarized RPE sheets (cultured on an ultrathin parylene substrate) were made into a co-graft using bio-adhesives [gelatin, growth factor-reduced matrigel, and medium viscosity (MVG) alginate]. In vivo transplantation experiments were conducted in immunodeficient Royal College of Surgeons (RCS) rats at advanced stages of retinal degeneration. Structural reconstruction of the severely damaged retina was observed based on histological assessments and optical coherence tomography (OCT) imaging. Visual functional assessments were conducted by optokinetic behavioral testing and superior colliculus electrophysiology. Long-term survival of the co-graft in the rat subretinal space and improvement in visual function were observed. Immunohistochemistry showed that co-grafts grew, generated new photoreceptors and developed neuronal processes that were integrated into the host retina. This novel approach can be considered as a new therapy for complete replacement of a degenerated retina.https://www.frontiersin.org/articles/10.3389/fnins.2021.752958/fullretinal transplantationretinal degenerationhuman embryonic stem cells (hESCs)tissue engineeringvision testing |
| spellingShingle | Biju B. Thomas Biju B. Thomas Bin Lin Bin Lin Juan Carlos Martinez-Camarillo Juan Carlos Martinez-Camarillo Danhong Zhu Danhong Zhu Bryce T. McLelland Bryce T. McLelland Gabriel Nistor Hans S. Keirstead Mark S. Humayun Mark S. Humayun Magdalene J. Seiler Magdalene J. Seiler Magdalene J. Seiler Magdalene J. Seiler Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats Frontiers in Neuroscience retinal transplantation retinal degeneration human embryonic stem cells (hESCs) tissue engineering vision testing |
| title | Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats |
| title_full | Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats |
| title_fullStr | Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats |
| title_full_unstemmed | Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats |
| title_short | Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats |
| title_sort | co grafts of human embryonic stem cell derived retina organoids and retinal pigment epithelium for retinal reconstruction in immunodeficient retinal degenerate royal college of surgeons rats |
| topic | retinal transplantation retinal degeneration human embryonic stem cells (hESCs) tissue engineering vision testing |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.752958/full |
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