A study conducted by a so-called “therapeutic” cloning sponsor (Gènéthique press review of May 5th, 2014), published in Nature, compares human pluripotent stem cells and concludes that stem cells created by cloning are superior to the widely used iPS cells created by Nobel Prize winner, Professor Yamanaka. In reality, the article by Hong Ma et al. is a more balanced account than critics initially thought.
– directly from embryos produced by IVF with no cell reprogramming (IVF-ES) known more generally as embryo stem cells,
– by reprogramming carried out by nuclear transfer, in other words by so-called “therapeutic” cloning (NT-ES),
– and by reprogramming with transcription factors, i.e. today’s well known and widely used technique developed by Professor Yamanaka, Nobel Prize Winner for Medicine (iPS).
Protocol. IVF-ES and NT-ES cells were derived from oocytes taken from the same donor and were therefore genetically comparable. Conversely, iPS cells were derived from fœtal cutaneous fibroblasts, which limited the quality of comparison with the other two types of cells. The reprogrammed cells – NT-ES and iPS – were compared to non-programmed cells – FIV ES – (“traditional” embryo stem cells) to highlight genetic (duplications, deletions) and epigenetic 1 (differences in the methylation of DNA determining transcription differences, i.e. in the creation of proteins from DNA) anomalies, which could have been introduced by the reprogramming process.
Results The authors did not find any significant genetic differences between iPS and NT ES. At an epigenetic level, DNA methylation in the NT ES cells was more similar to that found in the iPS cells than the methylation in IVF-ES cells. This shows that reprogramming, whether carried out by genetic manipulation (iPS) or nuclear transfer (therapeutic cloning, NT ES) may trigger epigenetic anomalies due to incomplete programming. However, although iPS cells do not present a “specific type” of epigenetic anomaly which might also be found in NT ES, they have a greater number of epigenetic anomalies. These iPS cells, which were affected by incomplete demethylation (incomplete reprogramming) also possess gene transcription anomalies. Based on these observations, Hong Ma, Shoukhrat Mialipov et al. deduced that reprogramming by nuclear transfer seems more effective and more complete than genetic reprogramming based on the Yamanaka (iPS) technique.
… to be balanced. These conclusions call for a certain element of moderation in terms of their practical application: firstly because NT-ES and FIV-ES cells in this study have been harvested from oocytes taken from the same donor. Therefore, they were expected to be more similar than the iPS cells derived from fœtal skin cells. Secondly, because 30% of the iPS cells appear perfectly normal, which shows that iPS programming can be of excellent quality. Under these conditions, sorting can therefore be carried out amongst iPS cells to eliminate any anomalies. On the other hand, it should be noted that, in particular, the technical supremacy of cloning does not make any sense if ethical issues are disregarded. For Martin Pera, biologist specialising in stem cells and who studied pluripotency at Melbourne University in Australia, genetic reprogramming (iPS) is still the most widely used stem cell technique. “The nuclear transfer technique used to obtain cloned embryo stem cells is more difficult from an ethical, logistic and technical standpoint:In fact, women must give their ovules to create an embryo which will have to be destroyed for research purposes“.
N.B. Gènéthique: the second article of the lettre mensuelle de mai 2014 recommended further clarification regarding so-called “therapeutic” cloning.
 “Epigenetics” is the process for controlling gene activity in the genome, ranging from activation to silencing of the various genes present in the genome in order to satisfy the body’s requirements (e.g. throughout embryo development). This activation or silencing is carried out by DNA methylation or demethylation in the gene or genes in question. DNA methylation silences a gene whereas DNA demethylation activates a gene. This “epigenetic” control of the genome conditions the transcription activity of the genome (which depends on the genes’ waking state).