2014
DOI: 10.1038/srep03844
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Therapeutic potential of somatic cell nuclear transfer for degenerative disease caused by mitochondrial DNA mutations

Abstract: Induced pluripotent stem cells (iPSCs) hold much promise in the quest for personalised cell therapies. However, the persistence of founder cell mitochondrial DNA (mtDNA) mutations limits the potential of iPSCs in the development of treatments for mtDNA disease. This problem may be overcome by using oocytes containing healthy mtDNA, to induce somatic cell nuclear reprogramming. However, the extent to which somatic cell mtDNA persists following fusion with human oocytes is unknown. Here we show that human nuclea… Show more

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Cited by 18 publications
(10 citation statements)
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“…The chromosome-spindle complex is a fragile structure that needs to be handled with utmost care, as the DNA is not as stable as in pronuclei. Recently, another group has advised that the first polar body be removed along with the spindle from the donor oocyte before the procedure, as the polar body can be resorbed during later fusion of the karyoplast, and cause polyploidy (Greggains et al, 2014). Another disadvantage is that chromosome scattering can occur during metaphase II, and this evidence of spindle damage has previously been found to occur as a result of temperature fluctuation (Almeida and Bolton, 1995) and advanced maternal age (Battaglia et al, 1996).…”
Section: Mitochondrial Transfer Techniquesmentioning
confidence: 99%
See 1 more Smart Citation
“…The chromosome-spindle complex is a fragile structure that needs to be handled with utmost care, as the DNA is not as stable as in pronuclei. Recently, another group has advised that the first polar body be removed along with the spindle from the donor oocyte before the procedure, as the polar body can be resorbed during later fusion of the karyoplast, and cause polyploidy (Greggains et al, 2014). Another disadvantage is that chromosome scattering can occur during metaphase II, and this evidence of spindle damage has previously been found to occur as a result of temperature fluctuation (Almeida and Bolton, 1995) and advanced maternal age (Battaglia et al, 1996).…”
Section: Mitochondrial Transfer Techniquesmentioning
confidence: 99%
“…Although ethically challenging, this method could offer patients already suffering from mtDNA disease a novel treatment option. Since induced pluripotent stem cells (iPSCs) from these patients would still contain mutated mtDNA, stem cells could be harvested from embryos produced through somatic cell nuclear transfer to donor oocytes, which carry healthy mitochondria (Greggains et al, 2014). Using adult skin and amnion fibroblasts, a recent report has demonstrated that human nuclear transfer (NT) embryos contain very low levels of somatic cell mtDNA, with heteroplasmy levels below those found in MII spindle transfer human embryos (Greggains et al, 2014).…”
Section: Conluding Remarks and Prospectivesmentioning
confidence: 99%
“…Aged somatic cells might show high susceptibility to nuclear and mitochondrial genome instability [100]. Hypothetically, in reprogrammed somatic cells from patients to generate pluripotent stem cells for therapeutic application, mtDNA mutations of the somatic cell must be evaluated, including analysis of a broad spectrum of degenerative diseases associated with mutations in mtDNA, which are unlikely to be amenable to iPSCbased therapies due to the persistence of the somatic cell mtDNA mutations [101]. Furthermore, mature oocytes contain more than 150, 000 copies of mtDNA, which is at least an order of magnitude greater than the number in most somatic cells, and sperm contain only approximately 100 copies [102].…”
Section: Mitochondrial Featuresmentioning
confidence: 99%
“…Membrane fusion is facilitated by inactivated Sendai virus or an electrical pulse [35,36]. However, the latter is not well tolerated by human oocytes and zygotes [37,38]. The experiments of McGrath and Solter [35] revealed that PNT between zygotes from different mouse strains can produce healthy and normally reproducing offspring.…”
Section: Uncoupling the Inheritance Of Nuclear And Mtdna To Prevent Transmission Of Mtdna Diseasementioning
confidence: 99%