Therapeutic potential of somatic cell nuclear transfer for degenerative disease caused by mitochondrial DNA mutations.
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 nuclear transfer (NT) embryos contain very low levels of somatic cell mtDNA. In light of a recent report that embryonic stem cells can be derived from human NT embryos, our results highlight the therapeutic potential of NT for mtDNA disease, and underscore the importance of using human oocytes to pursue this goal.
1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK [3] Department of Gynecology, Oslo University Hospital, Rikshospitalet, Oslo 0027, Norway.
Gareth D
GD
Greggains
1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK.
Lisa M
LM
Lister
Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Helen A L
HA
Tuppen
1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK.
Qi
Q
Zhang
1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK.
Louise H
LH
Needham
1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK.
Nilendran
N
Prathalingam
1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK.
Louise A
LA
Hyslop
Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Lyndsey
L
Craven
Department of Genetics and Evolution, Institute of Zoology, Jagiellonian University, ul. Gronostajowa 9, 30-387 Krakow, Poland.
Zbigniew
Z
Polanski
1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK.
Alison P
AP
Murdoch
Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Douglass M
DM
Turnbull
1] Wellcome Centre for Mitochondrial Research, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK [2] Newcastle Fertility Centre, Centre for Life, Times Square, Newcastle upon Tyne, UK.
Mary
M
Herbert
D000650:Amnion / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics; D002478:Cells, Cultured; D065150:Cellular Reprogramming; D004272:DNA, Mitochondrial / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000628:therapy*; D053652:Nuclear Transfer Techniques; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000378:metabolism
D004272:DNA, Mitochondrial