Two new techniques might make it possible to derive stem cells from embryos without destroying them 鈥� possibly offering an 鈥渆thical鈥� way of harvesting stem cells.
The advances, both published online in Nature, appear to overcome the key moral objection to the use of ESCs in medicine 鈥� the fact that the cells can only be obtained by destroying a human embryo, usually a 鈥渟pare鈥� left over from infertility treatment. The hope is that the cells, which can develop into any cell type in the body, could one day be used to regenerate new tissues or organs for patients.
To date, almost all human ESCs have been obtained by taking a human embryo and growing it into a ball of about 100 cells which contains a so-called 鈥渋nner cell mass鈥� rich in the precious ESCs. Once the ESCs have been removed with a syringe, the embryo effectively perishes.
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Bob Lanza and his colleagues at Advanced Cell Technology, a company in Worcester, Massachusetts, US, overcame this problem in mice by extracting just one cell from a very early 8-cell embryo called a morula. Lanza and his colleagues coaxed the single extracted cell, called a blastomere, into dividing into a colony of ESCs.
They did this by putting the blastomere in contact with pre-existing ESCs. These provided the correct signals for the blastomere to become a stem cell too.
Routine procedure
But the key benefit of this technique may be that the remaining 7-cell embryos, when implanted into the wombs of female mice, developed into completely normal baby mice. Of the 47 implanted, 23 came to term, exactly the same rate as for 鈥渃ontrol鈥� 8-cell morulas that had not had a blastomere removed.
鈥淚t means we overcome the key pro-life objection, that you must destroy life to save life,鈥� says Lanza. Also, he says that the technique used to extract the blastomere is identical to that used routinely in pre-implantation diagnosis during IVF to screen out embryos which are defective and have no chance of surviving. 鈥淭his procedure has been done hundreds of thousands of times, so we know it has a minimal or negligible effect on the embryo,鈥� he says.
Now the race is on to try the technique in humans, and the intention is to attempt it first on non-viable embryos selected during pre-implantation diagnosis, during which a blastomere would be extracted anyway.
Exact tissue match
The second technique, dubbed 鈥渁ltered nuclear transfer鈥� or ANT and developed by Rudolf Jaenisch and Alexander Meissner at the MIT鈥檚 Whitehead Institute in Boston, Massachusetts, overcomes a slightly different ethical objection, that of extracting ESCs from transient cloned 鈥渆mbryos鈥�.
These are created from a patient鈥檚 鈥渄onor鈥� cell, a skin cell for example, merged with a human egg emptied of its own nucleus. This forms an embryo similar to that from which Dolly the cloned sheep was produced, and has the potential to provide an exact tissue match for the patient.
The objection to this, again, is that an 鈥渆mbryo鈥� capable of becoming the twin of the patient if implanted into the womb has to be destroyed in order to obtain the ESCs needed to treat the patient.
Jaenisch and Meissner got round this in mice by infecting the 鈥渄onor鈥� skin cell with a virus. This blocks the action of Cdx2, a gene essential for formation of the placenta. Only then was the skin cell merged with an egg, creating an entity unable to be implanted in the womb, and therefore not 鈥渜ualifying鈥� as a true embryo.
鈥淧olitically na茂ve鈥�
鈥淲e took away the potential for the skin cell to become an embryo,鈥� says Jaenisch. If it is not an embryo, it cannot be 鈥渒illed鈥� to obtain the stem cells, they reason.
Jaenisch鈥檚 technique also allowed the activity of the Cdx2 gene to be restored in ESCs extracted from the 鈥減seudo-embryo鈥�. An enzyme applied to the cells stripped out the virus which had blocked Cdx2 in the skin cell, so the ESCs obtained were completely normal and functional.
Both Lanza and Jaenisch insist that their new techniques should not be portrayed as alternatives to existing techniques, and that all existing lines of research should continue.
But not everyone is as sanguine. 鈥淚t is politically naive to talk about alternatives, and this terminology undermines the moral stance of scientists pursuing the other techniques,鈥� says Arthur Caplan of the Center for Bioethics at the University of Pennsylvania. 鈥淚f you hint that it might solve the moral dispute, you鈥檙e providing ammunition for opponents, so it鈥檚 essential to back the original stance,鈥� he says.
Journal reference : Nature (DOI: 10.1038/nature04277 and DOI: 10.1038/nature04257)
