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...

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Detalles Bibliográficos
Autores principales: Kemp, Kevin, Dey, Rimi, Cook, Amelia, Scolding, Neil, Wilkins, Alastair
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
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.
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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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