Cargando…
MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus
Kernicterus is a permanent condition caused by brain damage from bilirubin toxicity. Dystonia is one of the most debilitating symptoms of kernicterus and results from damage to the globus pallidus (GP). One potential therapeutic strategy to treat dystonia in kernicterus is to replace lost GP neurons...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125107/ https://www.ncbi.nlm.nih.gov/pubmed/35596532 http://dx.doi.org/10.1177/09636897221101116 |
_version_ | 1784711877442404352 |
---|---|
author | Yang, Fu-Chen Vivian, Jay L. Traxler, Catherine Shapiro, Steven M. Stanford, John A. |
author_facet | Yang, Fu-Chen Vivian, Jay L. Traxler, Catherine Shapiro, Steven M. Stanford, John A. |
author_sort | Yang, Fu-Chen |
collection | PubMed |
description | Kernicterus is a permanent condition caused by brain damage from bilirubin toxicity. Dystonia is one of the most debilitating symptoms of kernicterus and results from damage to the globus pallidus (GP). One potential therapeutic strategy to treat dystonia in kernicterus is to replace lost GP neurons and restore basal ganglia circuits through stem cell transplantation. Toward this end, we differentiated human embryonic stem cells (hESCs) into medial ganglion eminence (MGE; the embryological origin of most of the GP neurons)-like neural precursor cells (NPCs). We determined neurochemical phenotype in cell culture and after transplanting into the GP of jaundiced Gunn rats. We also determined grafted cell survival as well as migration, distribution, and morphology after transplantation. As in the GP, most cultured MGE-like NPCs expressed γ-aminobutyric acid (GABA), with some co-expressing markers for parvalbumin (PV) and others expressing markers for pro-enkephalin (PENK). MGE-like NPCs survived in brains at least 7 weeks after transplantation, with most aggregating near the injection site. Grafted cells expressed GABA and PV or PENK as in the normal GP. Although survival was low and the maturity of grafted cells varied, many cells produced neurite outgrowth. While promising, our results suggest the need to further optimize the differentiation protocol for MGE-like NPC for potential use in treating dystonia in kernicterus. |
format | Online Article Text |
id | pubmed-9125107 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-91251072022-05-24 MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus Yang, Fu-Chen Vivian, Jay L. Traxler, Catherine Shapiro, Steven M. Stanford, John A. Cell Transplant Original Article Kernicterus is a permanent condition caused by brain damage from bilirubin toxicity. Dystonia is one of the most debilitating symptoms of kernicterus and results from damage to the globus pallidus (GP). One potential therapeutic strategy to treat dystonia in kernicterus is to replace lost GP neurons and restore basal ganglia circuits through stem cell transplantation. Toward this end, we differentiated human embryonic stem cells (hESCs) into medial ganglion eminence (MGE; the embryological origin of most of the GP neurons)-like neural precursor cells (NPCs). We determined neurochemical phenotype in cell culture and after transplanting into the GP of jaundiced Gunn rats. We also determined grafted cell survival as well as migration, distribution, and morphology after transplantation. As in the GP, most cultured MGE-like NPCs expressed γ-aminobutyric acid (GABA), with some co-expressing markers for parvalbumin (PV) and others expressing markers for pro-enkephalin (PENK). MGE-like NPCs survived in brains at least 7 weeks after transplantation, with most aggregating near the injection site. Grafted cells expressed GABA and PV or PENK as in the normal GP. Although survival was low and the maturity of grafted cells varied, many cells produced neurite outgrowth. While promising, our results suggest the need to further optimize the differentiation protocol for MGE-like NPC for potential use in treating dystonia in kernicterus. SAGE Publications 2022-05-20 /pmc/articles/PMC9125107/ /pubmed/35596532 http://dx.doi.org/10.1177/09636897221101116 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Article Yang, Fu-Chen Vivian, Jay L. Traxler, Catherine Shapiro, Steven M. Stanford, John A. MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus |
title | MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus |
title_full | MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus |
title_fullStr | MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus |
title_full_unstemmed | MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus |
title_short | MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus |
title_sort | mge-like neural progenitor cell survival and expression of parvalbumin and proenkephalin in a jaundiced rat model of kernicterus |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125107/ https://www.ncbi.nlm.nih.gov/pubmed/35596532 http://dx.doi.org/10.1177/09636897221101116 |
work_keys_str_mv | AT yangfuchen mgelikeneuralprogenitorcellsurvivalandexpressionofparvalbuminandproenkephalininajaundicedratmodelofkernicterus AT vivianjayl mgelikeneuralprogenitorcellsurvivalandexpressionofparvalbuminandproenkephalininajaundicedratmodelofkernicterus AT traxlercatherine mgelikeneuralprogenitorcellsurvivalandexpressionofparvalbuminandproenkephalininajaundicedratmodelofkernicterus AT shapirostevenm mgelikeneuralprogenitorcellsurvivalandexpressionofparvalbuminandproenkephalininajaundicedratmodelofkernicterus AT stanfordjohna mgelikeneuralprogenitorcellsurvivalandexpressionofparvalbuminandproenkephalininajaundicedratmodelofkernicterus |