Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

In one of this year’s biggest medical breakthroughs, ‘scientists’ from Portland, Oregon reported a new method about reprogramming somatic cells to human embryonic stem cells through a technique called ‘somatic cell nuclear transfer (SCNT)’. The discovery was so phenomenal, Cell journal accepted it within four days of submission.

Reprogramming somatic cells into pluripotent embryonic stem cells (ESCs) by somatic cell nuclear transfer (SCNT) has been envisioned as an approach for generating patient-matched nuclear transfer (NT)-ESCs for studies of disease mechanisms and for developing specific therapies. Past attempts to produce human NT-ESCs have failed secondary to early embryonic arrest of SCNT embryos. Here, we identified premature exit from meiosis in human oocytes and suboptimal activation as key factors that are responsible for these outcomes. Optimized SCNT approaches designed to circumvent these limitations allowed derivation of human NT-ESCs. When applied to premium quality human oocytes, NT-ESC lines were derived from as few as two oocytes. NT-ESCs displayed normal diploid karyotypes and inherited their nuclear genome exclusively from parental somatic cells. Gene expression and differentiation profiles in human NT-ESCs were similar to embryo-derived ESCs, suggesting efficient reprogramming of somatic cells to a pluripotent state.

Several experts commented on how ground-breaking the discovery is.

Expert reaction to human embryonic stem cells derived by somatic cell nuclear transfer

For example, Professor Robin Lovell-Badge, Head of Developmental Genetics, MRC National Institute for Medical Research, said:

The scientists responsible for the latest work managed to overcome many of the technical problems experienced previously by others, making each step more efficient, and found that therapeutic cloning could work very successfully. This means that although early human embryo development is slightly different from that of other animals, including monkeys, we are not that unique.

That is true, but the ‘scientists’ responsible for the published work were apparently not able to overcome few other technical problems, such as those related to image duplication and biological vs technical replicates. Readers reviewed the paper post-publication and reported several anomalies. Please check the post-publication review by peer 1, as reproduced below.

This paper reports the novel creation of human embryonic stem cells from somatic nuclei. It has received massive media coverage and is surely pencilled in as a strong candidate for scientific publication of the year.

It does however have several examples of image reuse which might be of interest to PubPeer members and readers.

- Fig. 2F is a slightly cropped version of the cell microscopy image in Fig. 6D top left.

- Fig. 6D top right, the cell microscopy image is a slightly cropped version of supplementary Fig. s5, top right. The cells in 6D are labelled as “h-ESO- NT1 Ph” yet in figure s5 they are labelled to be “hESO-7”. We understand the former to inherit caffeine-treated somatic nuclei whereas the latter are original stem cells.

Under pressure to assemble the figures for rapid publication, one can understand making a cut and paste figure assembly mistake. Nevertheless it should be noted that image cropping does take extra work.

- Figure S6 top centre and top right are the same image.

- Figure S6 middle left and lower right are reported to be biological replicates of microarray expression quantitation. In those cases however the narrow spread indicates that the data are extremely similar and are only understandable as technical replicates (where the same RNA sample is hybridised to two different arrays). It is useful to do technical replicates to control experimental reproducibility, but biological replicates are more valuable when reporting results. They are not the same thing and should not be conflated. (For the record, we did check the microarray data deposited at Gene Expression Omnibus (GSE46397)).

Lastly we note that, in the paper, it is recorded that the journal Cell accepted this paper just 4 days after submission. Perhaps, under the circumstances, the pre-publication peer review had to be a little hasty? At least here at Pubpeer, while conducting post publication review, we can take as long as necessary to make up for that lost time.

In light of the above, should ‘pubpeer’ be deemed the biggest breakthrough in science?

Also check -

Stem-cell Cloner Acknowledges Errors in Groundbreaking Paper

“Whatever the explanation is, it’s amazing that there is another issue with a paper in SCNT [somatic-cell nuclear transplantation]. The four-day review process was obviously inadequate, says Arnold Kriegstein, director of the stem-cell programme at the University of California, San Francisco. It’s a degree of sloppiness that you wouldn’t expect in a paper that was going to have this high profile. One worries if there is more than meets the eye and whether there are other issues with the work that are not as apparent.

Six years ago, when Mitalipov created cloned embryonic stem cells in monkeys, editors at Nature forced him to wait some six months for publication until the feat was verified independently. Both the original paper and the confirmatory data were published together2, 3. This time, were a trusted lab. We had already shown our results were real, Mitalipov said.

Seems like rules are different for ‘trusted labs’. Oh well.