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Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina

Cell replacement therapies may be key in achieving functional recovery in neurodegenerative optic neuropathies diseases such as glaucoma. One strategy that holds promise in this regard is the use of human embryonic stem cell and induced pluripotent stem-derived retinal ganglion cells (hRGCs). Previo...

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Autores principales: Croteau, Louis-Philippe, Risner, Michael L., Wareham, Lauren K., McGrady, Nolan R., Chamling, Xitiz, Zack, Donald J., Calkins, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600680/
https://www.ncbi.nlm.nih.gov/pubmed/36291110
http://dx.doi.org/10.3390/cells11203241
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author Croteau, Louis-Philippe
Risner, Michael L.
Wareham, Lauren K.
McGrady, Nolan R.
Chamling, Xitiz
Zack, Donald J.
Calkins, David J.
author_facet Croteau, Louis-Philippe
Risner, Michael L.
Wareham, Lauren K.
McGrady, Nolan R.
Chamling, Xitiz
Zack, Donald J.
Calkins, David J.
author_sort Croteau, Louis-Philippe
collection PubMed
description Cell replacement therapies may be key in achieving functional recovery in neurodegenerative optic neuropathies diseases such as glaucoma. One strategy that holds promise in this regard is the use of human embryonic stem cell and induced pluripotent stem-derived retinal ganglion cells (hRGCs). Previous hRGC transplantation studies have shown modest success. This is in part due to the low survival and integration of the transplanted cells in the host retina. The field is further challenged by mixed assays and outcome measurements that probe and determine transplantation success. Thefore, we have devised a transplantation assay involving hRGCs and mouse retina explants that bypasses physical barriers imposed by retinal membranes. We show that hRGC neurites and somas are capable of invading mouse explants with a subset of hRGC neurites being guided by mouse RGC axons. Neonatal mouse retina explants, and to a lesser extent, adult explants, promote hRGC integrity and neurite outgrowth. Using this assay, we tested whether suppmenting cultures with brain derived neurotrophic factor (BDNF) and the adenylate cyclase activator, forskolin, enhances hRGC neurite integration, neurite outgrowth, and integrity. We show that supplementing cultures with a combination BDNF and forskolin strongly favors hRGC integrity, increasing neurite outgrowth and complexity as well as the invasion of mouse explants. The transplantation assay presented here is a practical tool for investigating strategies for testing and optimizing the integration of donor cells into host tissues.
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spelling pubmed-96006802022-10-27 Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina Croteau, Louis-Philippe Risner, Michael L. Wareham, Lauren K. McGrady, Nolan R. Chamling, Xitiz Zack, Donald J. Calkins, David J. Cells Article Cell replacement therapies may be key in achieving functional recovery in neurodegenerative optic neuropathies diseases such as glaucoma. One strategy that holds promise in this regard is the use of human embryonic stem cell and induced pluripotent stem-derived retinal ganglion cells (hRGCs). Previous hRGC transplantation studies have shown modest success. This is in part due to the low survival and integration of the transplanted cells in the host retina. The field is further challenged by mixed assays and outcome measurements that probe and determine transplantation success. Thefore, we have devised a transplantation assay involving hRGCs and mouse retina explants that bypasses physical barriers imposed by retinal membranes. We show that hRGC neurites and somas are capable of invading mouse explants with a subset of hRGC neurites being guided by mouse RGC axons. Neonatal mouse retina explants, and to a lesser extent, adult explants, promote hRGC integrity and neurite outgrowth. Using this assay, we tested whether suppmenting cultures with brain derived neurotrophic factor (BDNF) and the adenylate cyclase activator, forskolin, enhances hRGC neurite integration, neurite outgrowth, and integrity. We show that supplementing cultures with a combination BDNF and forskolin strongly favors hRGC integrity, increasing neurite outgrowth and complexity as well as the invasion of mouse explants. The transplantation assay presented here is a practical tool for investigating strategies for testing and optimizing the integration of donor cells into host tissues. MDPI 2022-10-15 /pmc/articles/PMC9600680/ /pubmed/36291110 http://dx.doi.org/10.3390/cells11203241 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Croteau, Louis-Philippe
Risner, Michael L.
Wareham, Lauren K.
McGrady, Nolan R.
Chamling, Xitiz
Zack, Donald J.
Calkins, David J.
Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina
title Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina
title_full Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina
title_fullStr Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina
title_full_unstemmed Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina
title_short Ex Vivo Integration of Human Stem Retinal Ganglion Cells into the Mouse Retina
title_sort ex vivo integration of human stem retinal ganglion cells into the mouse retina
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9600680/
https://www.ncbi.nlm.nih.gov/pubmed/36291110
http://dx.doi.org/10.3390/cells11203241
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