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Asexual Stem Cell Production

By Sean Henahan, Access Excellence

Washington, DC (2/5/02)- The parthenogenetic creation of primate embryos with subsequent production of stem cells suggests a new, perhaps somewhat less ethically controversial direction in research aimed at treating human diseases with stem cell-derived therapies. Meanwhile, cloning and stem cell research continue to develop at a dizzying pace.

Partheno-what?

Parthenogenesis is derived from the Greek words for 'virgin birth'. In modern biology, it refers to a form of reproduction in which an ovum develops into a new individual without having been fertilized. Many insect species are known to reproduce by natural parthenogenesis. Examples include aphids, bees and ants. In bees and ants, unfertilized eggs become drones.

Graphic (above): primate parthenogenetic embryos

As long ago as 1900, biologists were able to encourage artificial parthenogenesis in some species. Jacques Loeb reported in that year that he was able to induce unfertilized frog eggs to grow by scratching them with a needle. Since that time various chemical and mechanical means have been used to produce artificial parthenogenesis in numerous animals including rabbits. However, in most cases the resulting developments abnormal.

Athena in the Parthenon

While the ancient Greeks may have been mystified by many elements of molecular biology, they would have easily been able to grasp parthenogenesis, a concept rooted in their oldest myths.

athena with aegis

Graphic (above): Athena bearing the aegis

Athena, daughter of Zeus, was among the most important of the Greek deities. Her birth was most unusual. Zeus swallowed his first wife Thetis when she became pregnant, fearing a son would steal his throne. He developed a severe headache and his fellow god Hephaestus was good enough to split his head open with an ax. Athena emerged full grown, wearing a suit of armor, from the head of Zeus.

Athena was the patron goddess of Athens, and was associated with everything from warfare and urban development to fertility and weaving. Her animal symbol the owl gives rise to the still current association between owls and wisdom. The Parthenon is the name of the temple of Athena on the Acropolis. Other familiar words associated with Athena include the aegis (her shield) and palladium (from Pallas Athena). NASA's "Project Athena" is a K-12 global weather education project.

A team of well-respected scientists from Mayo Clinic, Sloan Kettering Cancer Center and Wake Forest University working with a Massachusetts biotechnology company announced that they had managed to create primate embryos parthenogenetically, that is, without fertilization. Moreover, they were able to tease stem cells derived from the asexually derived embryos to produce numerous types of cells including brain, heart and smooth muscle cells.

One particularly promising development was the report that the researchers were able to produce midbrain dopamine neurons, a first. The hope is that some day such cells could replace dysfunctional cells in the brains of patients with central nervous disorders such as Parkinson's disease and Huntington's disease.

Embryos are normally the product of sexual reproduction, when the male sperm and female egg combine DNA. The current research involved stimulating a monkey egg to grow without any help from sperm. The researchers used chemicals to signal the eggs not to eject half of their chromosomes (as they would do in sexual reproduction) and command the eggs to start dividing. In this case the resulting mass of 100 or so cells, known as the blastocyst, cannot become a viable organism when produced with the new technique. Four of 28 parthogenetic eggs developed into blastocysts. The researchers were able to derive a single stem cell line from one of the blastocysts. .

"Neurons and other cells derived from this renewable source could alleviate some of the technical problems of human cell therapy, including rejection of transplanted tissue." said Jose Cibelli, Ph.D., chief scientist at Advanced Cell Technologies.

Stem cells are the holy grail of modern biology. These root cells can, with proper stimulation, be used to produced virtually any type of cell in the body. Until now, the best source of stem cells has been human embryos. These have typically been obtained from fertility clinics. Considerable research is also underway to clone stem cells derived from non-embryonic tissue. The possibility of deriving stem cells from nonviable, asexually produced blastocysts might solve, at least for some, the ethical debate currently raging on the direction of therapeutic stem cell research..

"This study suggests an alternative to human therapeutic cloning. Differentiated cell types derived in vitro by parthenogenesis eliminate the requirement to produce or disaggregate a normal, competent embryo and may circumvent the ethical concerns voiced by some, positively impacting the debate in stem cell research," the researchers noted in Science.

Continuing Controversy

How long will it be before human parthenogenesis is achieved? Researchers from the same biotech company that supported the current research, Advanced Cell Technologies, created considerable controversy in November of last year when they announced they had cloned human embryos. The embryos had not grown beyond six cells and had not produced stem cells.

While the race is on to create parthenogenetic human embryos, considerable doubts remain regarding the safety and efficacy of this approach. Researchers believe that the male DNA that mixes with the females DNA in the egg probably has an important role to play in gene activation in at least some kinds of stem cells. For example, studies in mice produced parthenogenitically suggest that those stem cells differentiate more readily into neurons than into other cell types such a muscle. The hypothesis that such cells would indeed be immune-privileged also remains unproven.

Publish or ???

There are also increasing concerns that the rush to be first is weakening the safeguards provided by the traditional process of presenting data in peer-reviewed journals. In some cases (e.g. Dolly the cloned sheep) potentially earthshaking research findings are announced at press conferences rather than submitted to scientific journals. This may be a good way to get the attention of the venture capitalists (and stockholders) who support biotech startups, but does not allow the review process that has become part of process of communicating new scientific findings. Moreover, an initial publication in a journal has traditionally been considered a starting point, with other researchers withholding judgment until results can be reproduced independently.

Stem Cells Grow Human Blood Vessels

Efforts to derive stem cells from adult tissue are also progressing at a remarkable rate. A report from the University of Minnesota Stem Cell Institute indicates just how fast the field of therapeutic cloning is evolving. Researchers there announced that they have managed to get a hitherto unknown type of adult bone marrow stem cell to expand in the test tube into endothelial cells, and then to get those cells to engraft in mice and contribute to new growth of blood vessels.

"These lab results demonstrate the potential of adult bone marrow stem cells to differentiate beyond mesenchymal cells, into cells of the endothelium. What we have seen is the ability of these cells to feed the blood vessels of tumors and to heal the blood vessels surrounding wounds. The findings suggest that these adult stem cells may be an ideal source of cells for clinical therapy. For example, we can envision the use of these stem cells for therapies against cancer tumors by, for instance, introducing anti-angiogenesis genes. Or, they could be used to heal wounds such as ulcers or diabetic wounds or to treat atherosclerosis," said Catherine Verfaillie, M.D., director of the University of Minnesota Stem Cell Institute.

The parthenogenetic monkey research appears in the February 1 issue of the journal Science. The findings of Dr. Verfaillie et al. appear the February 1, 2002 issue of Journal of Clinical Investigation.

Graphic (below): From blastocysts to stem cell to blood vessel. click to enlarge

In other developments:

click me!

  • Scientists at Advanced Cell Technologies announced they had grown a cow kidney in the lab from bovine stem cell clones. The research has not appeared in a peer-reviewed journal.
  • Two groups reported cloning transgenic pigs that could reduce xenotransplant rejection.
  • Dolly, the sheep cloned from adult sheep cells, has arthritis. This raises concerns that such an approach is unsafe. No evidence exits linking the arthritis with the cloning procedure.
  • Japanese researchers reported in Science that mice cloned from a adult cells were indistinguishable from normal mice and were free of genetic defects.
  • Scientists at Aegen Biosciences announced they have built a chip that will automate the now laborious process of nuclear transfer used in cloning procedures.

 

 

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