BioEd Online

A California company has brought human cloning research to a new level with efficient production of cloned human blastocysts ? an early stage of embryos.

The company, Stemagen in La Jolla in California, hopes that its achievement will be the first step towards using cloning techniques for biomedical research and, potentially, therapy. But first they will need to go the next step ? using such blastocysts to establish self-propagating lines of embryonic stem cells that, as clones, would be genetically identical to a patient.

Cloned human blastocysts have been reported before, but not at this level of achievement. The five cloned blastocysts produced by Stemagen are the first ones to be made with adult human cells ? in this case male fibroblasts¹.

Korean researcher Woo Suk Hwang claimed in 2004 and 2005 to not only have created cloned human blastocysts, but also to have produced stem-cell lines from them. His results turned out to be fraudulent. In May 2005, Miodrag Stojkovic and his group at Newcastle University, UK, reported that three cloned embryos had made it to the blastocyst stage, but they could not produce a cell line. Stojkovic?s group used embryonic stem cells from discarded embryos from in vitro fertilization procedures, a less impressive achievement because these cells were already in a flexible embryonic state, and because they were not matched to any patient?s genetics.

Real, healthy clones?

Stojkovic, now at the Cellular Reprogramming Laboratory at Prince Felipe Research Centre in Valencia, Spain, and an associate editor at Stem Cells, says that this is a ?huge difference? from what his group had achieved. Stojkovic also congratulated the group for doing extensive genetic tests. One of the blastocysts successfully went through rigorous tests to prove its identity. ?After Hwang, the field is very sensitive,? says Stojkovic. ?With these analyses, there is no doubt that at least one is a real clone.?

Robert Lanza from Advanced Cell Technology in Los Angeles, California, a competitor in the field, says that the article lacks data to show that the cells were fully reprogrammed and that the resultant blastocysts were in good condition. He says the photos of the blastocysts ?look very unhealthy?.

Though most researchers have agreed not to use cloning techniques to produce human babies, there are fears that this sort of work might open the door to reproductive cloning says Marcy Darnovsky of the Center for Genetics and Society, a science watchdog group based in Oakland, California.

Good eggs

Lead author Andrew French credits the group?s success to the quality of the eggs they used. The company set up a laboratory next to a fertility centre and were able to get to work on eggs donated by women within two hours of extraction. Their 5 successful blastocysts came from 20-30 eggs.

Technologically there was nothing much new here, French admits. The team didn?t use the cutting-edge visualization technique that a group in Oregon claimed to be crucial for their success in creating an embryonic stem cell line from cloned monkey blastocysts, reported in November 2007 (see Cloned monkey stem cells produced). French says that there are no patents attached to their achievement. The company hopes to make money through agreements with drug companies that want access to specific stem-cell lines for different diseases.

Surprisingly, the group sent all five blastocysts out for independent DNA tests, foregoing a chance for the ultimate goal ? the establishment of a cloned embryonic stem-cell line. French says they wanted to ?make sure the right DNA was in the blastocyst? and rule out contamination. Since only 10-20% of such blastocysts are expected to produce cell lines, French says that he does not think they stood much of a chance anyway. ?We would have loved to go for the holy grail and get the stem-cell line, but we wanted to get this first step sorted out first,? he says.

Harvard stem-cell expert George Daley describes the article as an ?important first step? but he says the true test will be the derivation of cloned embryonic stem-cell lines.

Researchers in the field continue to take two parallel approaches to making patient-matched stem-cell lines. Some, like Stemagen, are using cloning; others are attempting to bypass eggs and embryos completely by instead reprogramming adult cells directly into embryonic-like stem cells.