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Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation

Human pluripotent stem cells have the capacity for directed differentiation into a wide variety of neuronal subtypes that may be useful for brain repair. While a substantial body of research has lead to a detailed understanding of the ability of neurons in fetal tissue grafts to structurally and fun...

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Autores principales: Denham, Mark, Parish, Clare L., Leaw, Bryan, Wright, Jordan, Reid, Christopher A., Petrou, Steven, Dottori, Mirella, Thompson, Lachlan H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311135/
https://www.ncbi.nlm.nih.gov/pubmed/22470319
http://dx.doi.org/10.3389/fncel.2012.00011
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author Denham, Mark
Parish, Clare L.
Leaw, Bryan
Wright, Jordan
Reid, Christopher A.
Petrou, Steven
Dottori, Mirella
Thompson, Lachlan H.
author_facet Denham, Mark
Parish, Clare L.
Leaw, Bryan
Wright, Jordan
Reid, Christopher A.
Petrou, Steven
Dottori, Mirella
Thompson, Lachlan H.
author_sort Denham, Mark
collection PubMed
description Human pluripotent stem cells have the capacity for directed differentiation into a wide variety of neuronal subtypes that may be useful for brain repair. While a substantial body of research has lead to a detailed understanding of the ability of neurons in fetal tissue grafts to structurally and functionally integrate after intra-cerebral transplantation, we are only just beginning to understand the in vivo properties of neurons derived from human pluripotent stem cells. Here we have utilized the human embryonic stem (ES) cell line Envy, which constitutively expresses green fluorescent protein (GFP), in order to study the in vivo properties of neurons derived from human ES cells. Rapid and efficient neural induction, followed by differentiation as neurospheres resulted in a GFP+ neural precursor population with traits of neuroepithelial and dorsal forebrain identity. Ten weeks after transplantation into neonatal rats, GFP+ fiber patterns revealed extensive axonal growth in the host brain, particularly along host white matter tracts, although innervation of adjacent nuclei was limited. The grafts were composed of a mix of neural cell types including differentiated neurons and glia, but also dividing neural progenitors and migrating neuroblasts, indicating an incomplete state of maturation at 10 weeks. This was reflected in patch-clamp recordings showing stereotypical properties appropriate for mature functional neurons, including the ability to generate action potentials, as well profiles consistent for more immature neurons. These findings illustrate the intrinsic capacity for neurons derived from human ES cells to integrate at a structural and functional level following transplantation.
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spelling pubmed-33111352012-04-02 Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation Denham, Mark Parish, Clare L. Leaw, Bryan Wright, Jordan Reid, Christopher A. Petrou, Steven Dottori, Mirella Thompson, Lachlan H. Front Cell Neurosci Neuroscience Human pluripotent stem cells have the capacity for directed differentiation into a wide variety of neuronal subtypes that may be useful for brain repair. While a substantial body of research has lead to a detailed understanding of the ability of neurons in fetal tissue grafts to structurally and functionally integrate after intra-cerebral transplantation, we are only just beginning to understand the in vivo properties of neurons derived from human pluripotent stem cells. Here we have utilized the human embryonic stem (ES) cell line Envy, which constitutively expresses green fluorescent protein (GFP), in order to study the in vivo properties of neurons derived from human ES cells. Rapid and efficient neural induction, followed by differentiation as neurospheres resulted in a GFP+ neural precursor population with traits of neuroepithelial and dorsal forebrain identity. Ten weeks after transplantation into neonatal rats, GFP+ fiber patterns revealed extensive axonal growth in the host brain, particularly along host white matter tracts, although innervation of adjacent nuclei was limited. The grafts were composed of a mix of neural cell types including differentiated neurons and glia, but also dividing neural progenitors and migrating neuroblasts, indicating an incomplete state of maturation at 10 weeks. This was reflected in patch-clamp recordings showing stereotypical properties appropriate for mature functional neurons, including the ability to generate action potentials, as well profiles consistent for more immature neurons. These findings illustrate the intrinsic capacity for neurons derived from human ES cells to integrate at a structural and functional level following transplantation. Frontiers Research Foundation 2012-03-22 /pmc/articles/PMC3311135/ /pubmed/22470319 http://dx.doi.org/10.3389/fncel.2012.00011 Text en Copyright: © 2012 Denham, Parish, Leaw, Wright, Reid, Petrou, Dottori and Thompson. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) , which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Neuroscience
Denham, Mark
Parish, Clare L.
Leaw, Bryan
Wright, Jordan
Reid, Christopher A.
Petrou, Steven
Dottori, Mirella
Thompson, Lachlan H.
Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation
title Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation
title_full Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation
title_fullStr Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation
title_full_unstemmed Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation
title_short Neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation
title_sort neurons derived from human embryonic stem cells extend long-distance axonal projections through growth along host white matter tracts after intra-cerebral transplantation
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311135/
https://www.ncbi.nlm.nih.gov/pubmed/22470319
http://dx.doi.org/10.3389/fncel.2012.00011
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