Human somatic cell nuclear transfer: Three genomes is the charm

Author: Angela C. H. McDonald, 10/06/11

Well before the creation of human induced pluripotent stem cells (iPSCs), a handful of researchers were using another reprogramming technique, somatic cell nuclear transfer (SCNT), with the hopes of deriving patient-specific pluripotent stem cell lines. The availability of such cell lines would open up immense potential for developing personalized cell-based therapies as well as allowing scientists to create models of complex diseases in a dish.

In the SCNT technique, the genetic material of an oocyte (unfertilized egg) is removed and replaced with the genetic material of an adult donor cell. This exchange stimulates a reprogramming event and results in an oocyte that contains the same genetic material as its adult donor. While SCNT has been done previously with human oocytes, researchers had not reported the generation of human embryonic stem cell (hESC) lines from SCNT-embryos. Until now.


Yesterday, Nature published a report describing the derivation of hESCs from SCNT-embryos.  However, there is a catch. These SCNT-hESCs have three sets of chromosomes.

Why do these SCNT-hESCs have three sets of chromosomes? The answer is in the experimental methods. Researchers, working out of a lab in New York, were not able to generate developing embryos using the classical SCNT technique. Instead, researchers combined the genetic material of a donor human skin cell (containing two sets of chromosomes) with a human oocyte (containing one set of chromosomes), thereby creating an oocyte with three sets of chromosomes. Cell division was then activated and a few days later the resulting embryo was used for hESC line derivation. While hESCs with three sets of chromosomes won’t be used therapeutically, this study is a huge step forward. Researchers can now use these SCNT-embryos to further understand SCNT and to optimize this technique for future therapeutic purposes.

SCNT has been slow to advance due to the difficulty of obtaining human oocytes for research. For this study, women participating in a reproductive oocyte donation program were given the option to choose to donate their oocytes to research. In total, 270 oocytes were obtained for SCNT experiments. The ability to obtain oocytes for research depends on location. Countries and even states differ in laws regulating the procurement and use of human oocytes for research. In New York, human oocytes can be used for research and donor compensation is permitted. Canada, in contrast, prohibits SCNT under the Assisted Human Reproductive Act with a maximum punishment of 10 years imprisonment and a fine of $500,000.

Why go through the trouble of SCNT if we can use iPSC technology to derive patient-specific pluripotent stem cells?  A number of benefits of SCNT have been proposed. One advantage of SCNT-hESCs is that they do not have an epigenetic memory. iPSCs can remember their cell type of origin and consequently, are biased in differentiation potential. SCNT-hESCs may also prove to be more useful when modeling epigenetic (DNA packaging) diseases. Additionally, SCNT research could be used to improve iPSC generation by identifying oocyte-reprogramming molecules that may enhance iPSC reprogramming.

 

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Angela C. H. McDonald

Angela C. H. McDonald

PhD candidate at Hospital for Sick Children
Angela is a PhD student in the Stem Cell and Developmental Biology program at the Hospital for Sick Children in Toronto. She is currently utilizing pluripotent stem cells to understand the genetic regulation of endoderm development. As an avid supporter of public science education, she co-founded the high school outreach initiative StemCellTalks sits on numerous public education committees including the International Society for Stem Cell Research Public Education Committee and the Stem Cell Network Public Outreach Committee.
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