Researchers have used altered nuclear transfer (ANT) to generate pluripotent murine embryonic stem (ES) cells from blastocysts inherently unable to implant in the uterus. Scientists hope the findings, published in the October 16 issue of
"This is just one possible approach using ANT, but this study provides the scientific basis for the conversation that could lead us to resolve our nation's impasse over ES cell research," William Hurlbut, from Stanford University, Ca., told
In another study, published in the same issue of
Working with mice, Rudolph Jaenisch and Alexander Meissner from the Massachusetts Institute of Technology in Cambridge, Mass. created blastocysts unable to express the gene Cdx2. Cdx2 is known for its crucial role in the formation of the trophectoderm, which gives rise to the placenta.
"By silencing the expression of Cdx2 before nuclear transfer, our goal was to create a cellular system unable to establish the basic body pattern of a human embryo, but able to generate fully functional ES cells," said Meissner.
To do so, the researchers infected murine fibroblasts with a conditional lentiviral RNA interference (RNAi) construct targeting Cdx2. After nuclear transfer, the resulting blastocysts generated ES cells in vitro, but were unable to implant when transferred in the uterus.
"This procedure isn't only interesting for its potential applications in humans," Meissner told
Because the modified ES cells' developmental potency was diminished compared to control cells, the team restored normal Cdx2 expression levels and pluripotency by transfecting a Cre plasmid targeting the RNAi construct.
"We've proved (ANT) works in mice, now there's a long road before anything can be tested with human cells," said Meissner. "We've first got to learn more about Cdx2 in humans."
Some scientists, however, oppose ANT, arguing that the technique could create additional technical hurdles and might not work in humans. "Practically, nuclear transfer is already a challenge in itself. Add genetic modifications, gene transduction - it's getting pretty heavy just to reach the same results," Bruno Peault, from the University of Pittsburg Medical Center, Pa., who did not participate in the study, told
While ANT received the endorsement of groups traditionally opposed to NT for ethical reasons, others remain unsatisfied. "I consider it's an abuse of science to use cloning to deliberately create crippled human embryos," Robert Lanza from Advanced Cell Technology in Worchester, Mass., who did not participate in the ANT study, told
In the same issue of