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 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.
['Kemp|Kevin|K|', 'Dey|Rimi|R|', 'Cook|Amelia|A|', 'Scolding|Neil|N|', 'Wilkins|Alastair|A|']
D002454:Cell Differentiation D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D005269:Femur D005621:Friedreich Ataxia D055785:Gene Knockdown Techniques D006706:Homeostasis D006801:Humans D006861:Hydrogen Peroxide D033862:Iron-Binding Proteins D059630:Mesenchymal Stem Cells D009569:Nitric Oxide D018384:Oxidative Stress D034741:RNA, Small Interfering D012583:Schwann Cells
Oxidative stress Frataxin Mesenchymal stem cells Friedreich’s ataxia