July 17, 2003
Frog Egg Cytoplasm Reprograms Adult Nuclei Into Embryonic State

Cambridge University researcher John Gurdon and colleagues have transplanted adult mouse and human nuclei into frogs eggs and found that frog egg cytoplasm has compounds in it that induce the production of Oct4 RNA which is normally expressed only in pluripotent embyonic stem cells.

When the researchers injected the adult nuclei into frog egg nucleii, rather than into the surrounding cytoplasm, Oct4 levels shot up by a factor of ten. "The reprogramming activity is particularly concentrated here," says Gurdon. Molecules in the frog nucleus may be responsible for the eggs' revitalizing abilities, he speculates

The researchers think there are compounds in frog oocytes that reprogram adult nuclei.

"We believe that the ability of amphibian oocyte components to induce stem cell gene expression in normal mouse and human adult somatic cells, and the abundant availability of amphibian oocytes, encourages the long-term hope that it may eventually be possible to directly reprogram cells, easily obtained from adult human patients, to a stem cell condition,"

Frog eggs are larger and much easier to work with. Also, since they are larger and have now been demonstrated to contain compounds that can cause mouse and human genomes to revert to a state more like the embryonic state it will be much easier for the scientists to isolate the compounds in the eggs that can do this. Trying to get enough human or mouse egg contents to fractionate and look for active compounds for this purpose would be much harder.

The obvious larger goal behind this research is to be able to take a sample of a person's cells, make those cells revert to an embryonic state. Those cells then would hold the potential to be coaxed into growing replacement organs or to supply various adult stem cell lines to replenish depleted aged stem cell reservoirs in the body.

Keep in mind that while a great deal of debate centers around whether human embryonic stem cell research should be allowed and in what ways it is ethical to acquire embryonic stem cells there is a great deal of research work on the state of other cell types that needs to be done to make useful therapies as well. Just as we need to understand better what exactly defines an embryonic stem cell or how to make a cell become an embryonic stem cell we also need to understand how cells become and maintain their state as other cell types.

Imagine you wanted to take some embryonic stem cells and convert them into liver cells in order to grow a new liver. Cells converted from one cell type to another cell type using some manipulation may be converted to a state that makes them seem like liver cells. But since they would not have experienced the exact sequence of signals and timings of signals that cells would experience in a developing embryo they may in some subtle way be different than liver cells in the regulatory state of their genes. Then the one potential danger is that they might revert to an embryonic state or convert into cancer cells or become some other undesired cell type.

See also the Better Humans report on this for other relevant links.

This report comes on the heels of the discovery of the gene Nanog which can turn adult cells into embryonic stem cells.

Share |      Randall Parker, 2003 July 17 10:21 PM  Biotech Organ Replacement

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