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Thanks to a recently published procedure (Hwang et al., 2005), generating genetically tailored human embryonic stem cell lines is now possible with reasonable efficiency by transferring a somatic cell nucleus of the desired genetic background into an enucleated oocyte. This resets the clock of the somatic nucleus to its embryonic state by an unknown mechanism that scientists are eager to understand. The technology, however, is at the core of the embryonic stem cell debate because it involves the destruction of the blastocyst formed from the manipulated oocyte. In addition, reliance on human oocytes is itself a source of ethical and logistical concerns.

Kevin Eggan and Chad Cowan, at Harvard University, sought an approach that would bypass this major issue. If the cytoplasm of an oocyte can do the reprogramming job, they asked, what about cytoplasm from its next of kin, an embryonic stem cell?

To test this alternative, they mixed a previously derived embryonic stem cell line with a fibroblast line, each tagged with a drug-resistance marker, in the presence of polyethylene glycol to induce cell fusion, and followed with double drug selection to isolate rare hybrids of the two cell types (Cowan et al., 2005). These hybrids are tetraploids but present the phenotype and the two most coveted characteristics of embryonic stem cells: capacity for immortal growth and pluripotency. Genome-wide gene expression analysis confirmed that, at the level of transcription, the embryonic stem cell program can win out.

This procedure promises to be a powerful tool to study the molecular mechanisms of reprogramming adult cells to their embryonic state, a theme that Eggan is most interested in pursuing. In the short term, he sees the importance of optimizing the technique, and also developing it into a system in which cell fusion is more efficient and it is possible to monitor whether cells go toward an embryonic or a differentiated fate after cell fusion.

Of course, the question burning on many people's lips is whether this technique can replace nuclear transfer into oocytes. Amid the attention that the paper has generated in the popular press, Cowan and Eggan have been prompt to point out that nuclear transfer is still well ahead from a technical perspective. The major hurdle of the fusion approach will be removing from the tetraploid hybrid the genetic material that belongs to the acceptor embryonic cell—a technical challenge which Eggan's team will also try to tackle.

“What we were looking for was a better way to study reprogramming,” explains Eggan, “but there was also a realization that if this worked, one could imagine that based on this firm biological foundation, it might be possible to use embryonic stem cells themselves, even without understanding it, as a means to reprogram adult cells”. The groundwork has certainly been laid now, and the prospect of replacing oocytes by a renewable resource is generating a lot of enthusiasm in the field.