Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells
Friedreich’s ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich’s ataxia include drugs that improv...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498643/ https://www.ncbi.nlm.nih.gov/pubmed/28456899 http://dx.doi.org/10.1007/s12311-017-0860-y |
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author | Kemp, Kevin Dey, Rimi Cook, Amelia Scolding, Neil Wilkins, Alastair |
author_facet | Kemp, Kevin Dey, Rimi Cook, Amelia Scolding, Neil Wilkins, Alastair |
author_sort | Kemp, Kevin |
collection | PubMed |
description | Friedreich’s ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich’s ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich’s ataxia. Knockdown of frataxin protein expression to levels detected in patients with the disorder was achieved, leading to decreased cellular viability, increased susceptibility to hydrogen peroxide-induced oxidative stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell proliferation and differentiation. Bone marrow stem cells are being investigated extensively as potential treatments for a wide range of neurological disorders, including Friedreich’s ataxia. The potential neuroprotective effects of bone marrow-derived mesenchymal stem cells were therefore studied using our frataxin-deficient cell model. Soluble factors secreted by mesenchymal stem cells protected against cellular changes induced by frataxin deficiency, leading to restoration in frataxin levels and anti-oxidant defences, improved survival against oxidative stress and stimulated both cell proliferation and differentiation down the Schwann cell lineage. The demonstration that mesenchymal stem cell-derived factors can restore cellular homeostasis and function to frataxin-deficient cells further suggests that they may have potential therapeutic benefits for patients with Friedreich’s ataxia. |
format | Online Article Text |
id | pubmed-5498643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-54986432017-07-21 Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells Kemp, Kevin Dey, Rimi Cook, Amelia Scolding, Neil Wilkins, Alastair Cerebellum Original Paper Friedreich’s ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich’s ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich’s ataxia. Knockdown of frataxin protein expression to levels detected in patients with the disorder was achieved, leading to decreased cellular viability, increased susceptibility to hydrogen peroxide-induced oxidative stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell proliferation and differentiation. Bone marrow stem cells are being investigated extensively as potential treatments for a wide range of neurological disorders, including Friedreich’s ataxia. The potential neuroprotective effects of bone marrow-derived mesenchymal stem cells were therefore studied using our frataxin-deficient cell model. Soluble factors secreted by mesenchymal stem cells protected against cellular changes induced by frataxin deficiency, leading to restoration in frataxin levels and anti-oxidant defences, improved survival against oxidative stress and stimulated both cell proliferation and differentiation down the Schwann cell lineage. The demonstration that mesenchymal stem cell-derived factors can restore cellular homeostasis and function to frataxin-deficient cells further suggests that they may have potential therapeutic benefits for patients with Friedreich’s ataxia. Springer US 2017-04-29 2017 /pmc/articles/PMC5498643/ /pubmed/28456899 http://dx.doi.org/10.1007/s12311-017-0860-y Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Paper Kemp, Kevin Dey, Rimi Cook, Amelia Scolding, Neil Wilkins, Alastair Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells |
title | Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells |
title_full | Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells |
title_fullStr | Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells |
title_full_unstemmed | Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells |
title_short | Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells |
title_sort | mesenchymal stem cell-derived factors restore function to human frataxin-deficient cells |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498643/ https://www.ncbi.nlm.nih.gov/pubmed/28456899 http://dx.doi.org/10.1007/s12311-017-0860-y |
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