Britains House of Lords final approval of therapeutic human cloning and embryonic stem cells research has intensified the battle for ascendancy between adult and embryonic stem cells. In the latest skirmish, two rapid online publications are presented as if they were evidence against the existence of adult stem cells. Dr. Mae-Wan Ho and Prof. Joe Cummins review the findings and expose the continuing campaign to mislead the public.
Two reports appeared as advance online publications in the top British journal Nature, accompanied by a news report that begins, "The hyped ability of adult stem cells to sprout replacement tissue types is being called into question. They may instead be fusing with existing cells, creating genetically mixed-up tissues with unknown health effects" . This leaves one with the distinct impression that adult stem cells might not exist, and furthermore, they may be a health hazard. What did they actually find?
In the first report , researchers from Edinburgh and Oxford took cells from the mouse brain marked with transgene 1, and cultured them together with ES cells marked with a second transgene, 2. They found that transgene 1 ended up in undifferentiated stem cells still carrying transgene 2. The explanation must be that the cells have fused together. This was confirmed by examining the cells chromosomes and identifying the distinctive chromosomes from both mouse lines. The hybrid cells carrying four sets of chromosomes (instead of the usual two) behaved as stem cells when injected into mouse embryos. Fusion could also be obtained between ES cells and cells isolated from adult brain. The frequency of fusion is between one in 10 000 to one in 100 000 brain cells, which is rather low. The suggestion is that the epigenetic reprogramming following cell fusion could "underlie many observations otherwise attributed to an intrinsic plasticity of tissue stem cells".
In the second report , mouse bone marrow cells marked with green fluorescent protein were found to fuse with ES cells in culture in the presence of the cytokine, interleukin-3, which is known to encourage cell fusion. The fused cells were found to have 4 to six sets of chromosomes by DNA analysis, and they behaved as ES cells when tested. These researchers pointed out that the spontaneous fusion rate (without interleukin-3) was extremely low, between 2-11 per million bone marrow cells, and is unlikely to account for all the findings with adult stem cells. "Some in vivo transplantation studies have reported robust (35-50%) levels of transdifferentiation, which makes it unlikely that the results are due to cell fusion events."
In fact, the senior authors in both reports admit that some adult stem cells may genuinely revert to an earlier stage of development or switch fates .
Neither report cited a paper published last year in the journal Blood, where a group from the Stem Cell Institute, Department of Medicine, and Cancer Center, University of Minnesota Medical School, Minneapolis, reported the most comprehensive experiments proving that a single adult stem cell can differentiate into all cell types in culture. By manipulating the media and culture conditions, different developmental fates were elicited. The cells could be made to differentiate into bone forming cells, cartilage forming cells, fat cells, skeletal muscle cells and endothelial cells.
The finding that adult cells can fuse with ES cells is therefore irrelevant to the debate, and the fact that it was used in an attempt to discredit adult stem cells is itself revealing, particularly in view of other recent findings on ES cells.
This latest anti-publicity on adult stem cells comes on the heels of a paper announcing success in embryonic stem (ES) cell transplant in a Parkinson rat model published in the house journal of the United States National Academy of Sciences . Neither the title of the paper, nor the abstract mentioned that in the experiment, five out of 25 rats receiving the transplant died with "teratoma-like tumors" in their brains, a well-known hazard of ES cells. In a further six of the rats, the graft "did not survive", though the paper did not specify how they found that out. Five rats that "did not receive full behavioral testing was analysed histologically". The behavioral improvement was a modest 40% in the rats that were tested.
In the current issue of the same journal , researchers compared the frequency and type of mutation induced in embryonic stem cells and embryonic somatic cells. They found that the spontaneous mutation frequency in ES cells is 100-fold lower than that in mouse embryonic fibroblasts (a somatic cell line), which is similar to adult cells in vivo. This could offer comfort to proponents of ES cells.
But, although the mutation frequency of genes was much lower in ES cells, mutant ES cells accumulated with time in culture. Furthermore, chromosome loss or duplication is the predominant mechanism of spontaneous mutation in ES cells, which was not detected in the fibrobasts. This confirms earlier reports of epigenetic instability and genomic instability in ES cells. The researchers warn, "These findings raise a concern regarding the use of stem cells that have been maintained in long-term culture for therapeutic purposes." It is not an argument against the therapeutic use of stem cells, they hastened to add, but rather indicates the need for screening such cultures to ensure the absence of chromosomal abnormalities.
Clearly, there are risks that ES cells may have a fundamental propensity towards chromosome instability and towards teratoma cancer. These should not be downplayed in attempts to promote ES cells.
We still see no need to support therapeutic human cloning and ES cells research.
One way for civil society to counter the House of Lords ruling is to refuse to give consent for their eggs and embryos to be used for research purposes.
Article first published 24/03/02
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