Editors' ChoiceStem Cells

Somatic Cell Nuclear Transfer Is All Grown Up

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Science Translational Medicine  07 May 2014:
Vol. 6, Issue 235, pp. 235ec82
DOI: 10.1126/scitranslmed.3009305

Technologies to reprogram the identity of adult somatic cells will open new avenues for disease modeling and personalized regenerative medicine. Morphing readily accessible adult somatic cells, such as blood and skin fibroblasts, into pluripotent stem cell lines either by transcription factors—induced pluripotent stem cells (iPSCs)—or somatic cell nuclear transfer (SCNT) into enucleated oocytes—SCNT human embryonic stem cells (hESCs)—should allow for advances in patient-specific care. Although SCNT works well in rodents, it has proven difficult to translate into human cells. In 2013, the laboratory of Mitalipov reported optimized techniques that enabled the generation of the first diploid human SCNT hESC lines. This was a major advance; however, the donor cells used were of fetal and early postnatal origin, so it remained unclear whether adult human cells could be efficiently reprogrammed by means of SCNT. Two recent papers from Chung et al. and Yamada et al. provide important confirmation that human cells can indeed be reprogrammed by means of SCNT to generate hESC lines. Moreover, both reports also demonstrate that adult human cells can be used to generate hESC lines by SCNT.

SCNT involves the transfer of a donor nucleus into an unfertilized enucleated egg. The eggs are then artificially activated to initiate developmental progression and reprogramming of the donor nucleus. When successful, the resulting SCNT embryo is a genetic “clone” of the somatic cell donor, with an identical complement of genomic, but not mitochondrial, DNA. Using distinct technical optimizations, both Chung et al. and Yamada et al. were able to generate diploid SCNT hESC lines with efficiencies of roughly 2 to 5%. The major advance in both papers was the first demonstrations of SCNT feasibility when using adult human donor cells. Excitingly, Yamada et al. also generated a SCNT hESC line from a female patient with type I diabetes and showed the ability to further differentiate this line into insulin-producing cells.

These studies provide new advances in the ability to generate patient-specific human pluripotent stem cell lines. Although there is evidence in rodents that SCNT may produce more genetically stable and epigenetically normal pluripotent stem cells lines than can iPSC-based techniques, this remains to be shown for human cells. Considering the technical and ethical constraints of using human eggs for SCNT, it will be especially important to rigorously evaluate and justify any advantages of SCNT over iPSC methodologies.

Y. G. Chung et al., Human somatic cell transfer using adult cells. Cell Stem Cell 10.1016/j.stem.2014.03.015 (2014). [Abstract]

M. Yamada et al., Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells. Nature 10.1038/nature13287 (2014). [Abstract]

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