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Mitochondrial mutations could hamper stem cell therapies

25 April 2016

By Dr Julia Hill

Appeared in BioNews 848

A study has found that stem cells from older people accumulate high numbers of mitochondrial DNA (mtDNA) mutations, which could limit their therapeutic value.

Most of a cell's DNA is contained in its nucleus, but a small proportion is located in its mitochondria, where the rate of mutation can be 10–20 times higher.

Professor Taosheng Huang, director of the Mitochondrial Medicine Program at Cincinatti Children's Hospital and one of the lead authors of the study, said: 'People tend to look just at the nuclear genome. But if you want to use induced pluripotent stem (iPS) cells in a human, you must check for mutations in the mitochondrial genome.'

Professor Huang's team originally sequenced the mtDNA of skin cells taken from a 72-year-old and found the overall level of mutations was low. But when they re-examined the cells individually, they discovered that the mtDNA mutation rate was highly variable between different cells, and in some cases it was so high that the mitochondria were unable to function properly.

As stem cell lines are created from individual cells, it is important that the originating cell is healthy, otherwise these defects could negate the benefits of stem cell treatments.

The team then created iPS cell lines from blood and skin cells of adults aged 24–72 and investigated the effects of age on mtDNA mutations. As they report in Cell Stem Cell, they found the stem cells of older people had much higher rates of mtDNA mutations than those from younger people.

Professor Huang suggested that it is therefore critical to create multiple iPS cell lines and sequence them individually for mtDNA mutations. Alternatively, it might be simpler just to use stem cells from younger adults, he wrote.

Dr Dieter Egli of the New York Stem Cell Foundation told Nature News that 'this is definitely going to have an impact' on clinical trials using iPSC cells, and that more screening of mtDNA would be needed for therapy. 'You can't just assume it does or doesn't work,' he said.

Mitochondrial defects are implicated in normal ageing, as well as in many age-related diseases, but Dr Egli added that it would be difficult to determine which mutations are meaningful. 'It's going to be very hard to find a cell line that's perfect,' he concluded.


01 August 2016 - by Annabel Slater 
A new stem cell treatment has reversed scarring in heart failure patients by 40 percent, and also improved recovery and survival, a small-scale trial has demonstrated...
18 July 2016 - by Dr Dusko Ilic 
A match of mitochondrial and nuclear genomes apparently affects healthy ageing in mice. But key questions need to be answered before stirring up implications for human mitochondrial replacement therapies...
11 July 2016 - by Dr Julia Hill 
The interaction between mitochondrial and nuclear DNA may have implications for health, metabolism and ageing, according to a new study...
04 July 2016 - by Dr Katie Howe 
Researchers have identified a gene that, when activated, causes mitochondria inherited from sperm to be destroyed shortly after fertilisation...
13 June 2016 - by Dr Özge Özkaya 
An extensive study examining human embryos created using mitochondrial donation has demonstrated that the technique does not adversely affect embryo development...

21 March 2016 - by Dr Julia Hill 
Scientists have created human stem cells with 23 chromosomes instead of 46, the normal number in a complete genome contained in almost all cells...
01 February 2016 - by Ryan Ross 
UK fertility doctors are seeking permission to trial a new IVF treatment that involves transferring additional mitochondria into egg cells before fertilisation...
25 January 2016 - by Dr Lanay Griessner 
A stem cell treatment routinely used for bone and blood cancers is showing promise at reversing the effects of multiple sclerosis...
20 July 2015 - by Dr Julia Hill 
Scientists in the USA have demonstrated how stem cell techniques may benefit people with incurable mitochondrial diseases. The research suggests it might be possible one day to replace diseased tissue in patients affected by the disorders...
27 April 2015 - by Antony Blackburn-Starza 
A gene-editing technique that may prevent mutated mitochondrial DNA from being passed down from mother to child has shown success in an animal study...

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