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Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)840-851
Number of pages12
JournalCerebellum
Volume16
Issue number4
Early online date29 Apr 2017
DOIs
DateAccepted/In press - 10 Apr 2017
DateE-pub ahead of print - 29 Apr 2017
DatePublished (current) - Aug 2017

Abstract

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.

    Research areas

  • Friedreich’s ataxia, Mesenchymal stem cells, Frataxin, Oxidative stress

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via SPRINGER at https://link.springer.com/article/10.1007%2Fs12311-017-0860-y#copyrightInformation. Please refer to any applicable terms of use of the publisher.

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