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Harnessing the Stem Cell Potential: The path to prevent mitochondrial disease

Nature Medicine volume 19, pages 1578–1579 (2013)Cite this article

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Although stem cells were initially thought to be the magic bullet for numerous diseases, translation of a stem cell–based cure into the clinic is still a work in progress. Basic research is shedding light into the potential of stem cells, and different research fronts are now exploring how to exploit this potential to tackle diverse conditions. In 'Bench to Bedside', Akemi Tanaka, Mark Sauer, Dieter Egli and Daniel Kort discuss how genome transfer from eggs of mothers with mutated mitochondria into an enucleated egg from a healthy female donor at an early developmental stage can eliminate mitochondrial disease. The negligible mutant mitochondrial DNA carryover and the differentiation of subsequent embryonic stem cells into various cell types with healthy mitochondrial DNA content suggest this could be used to prevent transmission of mitochondrial disease to the offspring. The authors discuss safety concerns and remaining technical questions that need to be resolved to make way for this new technology in the clinic. In 'Bedside to Bench', Nan Yang and Marius Wernig peruse a small study of children with a myelin disorder showing that transplantation of human neural stem cells leads to engraftment and donor cell–derived myelination.

Mutations in mitochondrial DNA (mtDNA) cause defects in respiratory chain function and energy production within mitochondria and result in a wide range of clinical conditions. Over 200 different mtDNA mutations have been identified and linked to phenotypes ranging from exercise intolerance to diabetes mellitus, respiratory failure, stroke, heart disease and neurodegenerative disorders. Clinical features and severity vary greatly depending on the specific mtDNA mutation, the percentage of mutant mtDNA per cell and the organ affected. Pathogenic mtDNA mutations are considered rare and largely affect children. They are found in approximately 1 in 200 live births1 and symptomatic disease is found in 1 out of 10,000 adults2, yet the actual incidence may be much higher given the diversity of clinical presentations and difficulty in securing a diagnosis. Advanced genomic techniques coupled with the expansion of the library of known mutations have increased physicians' ability to diagnose mitochondrial disorders, but treatment remains limited to symptomatic management. Translational research into mitochondrial disorders has been hindered by the unique features of human mitochondrial biology: maternal inheritance, the coexistence of both normal and mutated mtDNA in a single cell (genetic heteroplasmy) and rapid shifts in the proportion of mutant to normal mitochondrial genotypes during growth and development.

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Figure 1: Mitochondrial replacement to eliminate mutant mtDNA.

Katie Vicari

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Authors and Affiliations

  1. Akemi J. Tanaka is at the Department of Genetics, Yale University, New Haven, Connecticut, USA.,

    Akemi J Tanaka

  2. Mark V. Sauer and Daniel H. Kort are at the Center for Women's Reproductive Care, Columbia University, New York, New York, USA.,

    Mark V Sauer & Daniel H Kort

  3. Dieter Egli is at The New York Stem Cell Foundation Research Institute, New York, New York, USA.,

    Dieter Egli

Authors
  1. Akemi J Tanaka
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  2. Mark V Sauer
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  3. Dieter Egli
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  4. Daniel H Kort
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Correspondence to Dieter Egli.

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The authors declare no competing financial interests.

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Tanaka, A., Sauer, M., Egli, D. et al. Harnessing the Stem Cell Potential: The path to prevent mitochondrial disease. Nat Med 19, 1578–1579 (2013). https://doi.org/10.1038/nm.3422

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