Researchers may have come up with a new source of cells that could be used for nuclear transfer experiments and stem cell research. The research, reported in Nature, brings the prospect of therapeutically relevant, genetically tailored embryonic stem cell lines one step closer.
Until now, production of cloned animals and embryonic stem cell lines has relied on the use of unfertilized eggs - DNA is injected into a donor egg that has had its nucleus removed. However, Kevin Eggan and colleagues now show that fertilized eggs can also be used, suggesting that the activities required for genetic reprogramming persist after fertilization.
The team used newly fertilized mouse eggs in which cell division had been temporarily halted. The eggs' chromosomes were replaced with genetic material taken from mouse ES cells, yielding nine cloned animals. Of these, seven died from breathing difficulties, one died from a severe developmental defect and the last was rejected by its foster mother. To see if the method could be used to derive ES cells like those envisioned for patient-tailored stem cell therapies, they replaced the genetic material of fertilized mouse eggs with that of mature skin cells from mouse tails. These eggs divided to form blastocysts, and from these they were able to derive embryonic stem cells. They were also able to use defective zygotes as recipients to produce ES cells, suggesting that defective human zygotes available from IVF clinics could be used in this way.
Although the cloned animals' health is clearly a problem, suggesting that there were problems in nuclear reprogramming using this method, the study does indicate that early fertilized eggs or cells taken from them may eventually prove useful in creating patient-derived human embryonic stem cells. This is particularly important given the paucity of eggs available for cloning research and the controversy that surrounds egg donation.
Kevin Eggan (Harvard University, Cambridge, MA, USA)
Alan Colman (ES Cell International & A*STAR Institute of Medical Biology, Helios, Singapore)
(C) Nature press release.
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