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Parthenogenic Stem Cells

Parthenogenic Stem Cells

Wise Young, Ph.D., M.D.
W. M. Keck Center for Collaborative Neuroscience
Rutgers University, Piscataway, New Jersey 08854-8082

Cibelli, et al from Advanced Cell Technology (ACT), the company that attempted to clone human stem cells recently, reported the first successful isolation of parthenogenic stem cells. Parthenogenesis occurs when the egg is stimulated into thinking that it has been fertilized. Most cells in our body (somatic cells) have two sets of chromosomes (diploid), one from our father and one from our mother. Eggs and sperms only have one set of chromosomes (haploid or monoploid). When an egg is parthenogenically stimulated, the cells that result are monoploid.

This was originally reported in the news when the authors presented the work in a Los Angeles meeting several months ago. Several new details are now available.
1. The cells are from primates. It was not clear what species the cells came from.
2. Only 4 of 28 eggs reached blastocyst stage. This is not great but a reasonable yield.
3. They propagated the cells for 10 months (strongly suggesting that they are stem cells).
4. One of the eggs yielded a stable stem cell line (Cyno-1) which is also very important
5. The cells expressed high telomerase activity (characteristic of stem cells)
6. Chromosomal karotyping showed the right number of monoploid chromosomes for monkey
7. The stem cells produced dopaminergic neurons, cardiac, muscle, fat, and other cells.
8. Transplants of the cells produced teratomas that showed multiple tissues

In short, the cells are clearly stem cells, robust, and pluripotent. The finding the that cells produced dopaminergic neurons is of particularly interest because this is the cell type that one would want to produce to treat Parkinson's disease. Furthermore, they demonstrate that a monoploid stem cells can be pluripotent. When I first saw these results reported, I was wondering how robust and pluripotent these monoploid stem cells would. This study answered that question conclusively.

What is the significance of monoploidy? Well, somatic mammalian cells are diploid, i.e. have pairs of chromosomes. Diploid cells routinely shut off genes on one or the other chromosome. Unfortunately, if this occurred in monoploid cells, this could have disastrous consequences. The authors have shown that monoploid cells not only behave like stem cells and are pluripotent both in vivo and in vitro, but can transform into cell types that may be therapeutically relevant.

Parthenogenic stem cells do circumvent the false issue that was established by the House legislation HR2505 that bans nuclear transfer. They did not use nuclear transfer and therefore the cells would pass muster as a source of human embryonic stem cells. It is not a "clone" in the sense that it is monoploid but the genes would be the same. This method can be used only with women who have viable eggs. Men and older women would of course not be able to take advantage of these cells.

I would be curious to see how the anti-cloners would handle the new development. The only difference is that the original monoploid egg nucleus is left in place in the parthenogenic egg while the monoploid nucleus from the so-called "cloned" egg is replaced by a diploid nucleus from some other cell in the body. This is a very small difference.

The cloned egg and the parthenogenic egg are more similar than they are different. In both cases, a human egg would be used. In both cases, no fertilization was used and the eggs are stimulated to grow. In both cases the eggs are grown to blastocyst stage at which time the cells are harvested and the blastocyts are destroyed. In fact, the stimulus used to stimulate parthenogenesis is not so different from that used to stimulate the develop of the egg with the nuclear transfer.

In the coming months, as more scientists gain experience with the parthenogenic egg, we shall see if the results reported by Cibelli, et al. are robust and easy replicated. If so, this would provide an important source of monoploid stem cells for studies, allow systematic investigation of the differences between diploid and monoploid cells, and possibly provide a new source of stem cells for therapies.

Will monoploid stem cells be used for therapy? I think that the results are promising and these cells may well be appropriate for therapeutic use in humans. The technology exists today to collect many eggs from women. If many monoploid stem cell lines are developed, it may be possible to type them as we do for blood cells so reduce the likelihood of rejection, and then specifically matched cells can used. Alternatively, the cells may be genetically engineered to reduce the likelihood of rejection.

The results reported by Cibelli, et al. do not preclude the possibility that these monoploid cells behave abnormally after many divisions. But, this is a worry that is also present for diploid embryonic stem cells. The study shows clearly that monoploid stem cells do have the ability to form teratomas (multipotent tumors that show many different tissues).

Monoploid stem cells may provide some advantages over diploid stem cells. It seems, even with a first attempt at the task, one scientific group was able to obtained apparently normal appearing blastocysts from 4 of 28 eggs (a much higher percentage than those obtained with nuclear transfer). To date, nuclear transfer cloning has not yet been achieved in monkeys.

This discovery may well allow stem cell therapies that circumvent the restrictions of proposed legislation to ban human nuclear transfer in the United States. I hope, however, it is not used as an excuse to pass SR2505 which sets an unique precedent of criminalizing a critically important scientific tool, places the rights of blastocysts above those of living adults, and mistakenly asserts that reproductive cloning cannot be rigorously regulated without banning nuclear transfer.

Wise.



©Wise Young PhD, MD


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