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Genetic manipulations could be done directly on a culture of embryonic stem cells, and these altered cells subsequently used for nuclear transfer to an enucleated egg without the special manipulations that would have to be performed on a somatic cell culture.

Human Embryonic Stem Cells reported (ESS)

July 23, 1997

Human Fetal Cells Grown in Lab

NEW YORK (Reuters) -- For the first time, researchers have grown long-lived cultures of human embryonic cells with the capacity to develop into a wide range of tissues. The cells, taken from aborted human fetuses 5 to 8 weeks old, could find important medical uses if they can be turned into a supply of replacement tissue, or used as part of gene therapy. But there is some concern that the cells could also be used to create genetically-engineered humans. According to one of the researchers, Dr. John Gearhart, professor of gynecology and obstetrics at Johns Hopkins University School of Medicine in Baltimore, Maryland, the tissue taken from early pregnancy terminations contain "primordial germ cells"-- that eventually develop into reproductive organs, either ovaries or testes.

He notes that several years ago, researchers at the National Cancer Institute and at Vanderbilt University reported that mouse primordial germ cells grown in culture could yield cell lines that looked and had all the features of what are referred to as embryonic stem cells (ES cells) of the mouse. "So that's the procedure, in essence, that we've used," Gearhart says. "We have established cell lines that have all of the features that are ascribed to a pluripotential stem cell -- 'pluripotential' meaning it can differentiate potentially into any of the hundreds of cell types in the body."

"It's sort of like, 'the mother of all stem cells,"' the researcher explains. "It's a very early embryonic cell that can, under the right influences, go in any direction for differentiation." Gearhart says he and his colleagues are looking at studies in mice to point the way to successful genetic manipulation of human stem cells so that they differentiate into specific types of tissue cells. The fetal cells have been in culture for about nine months, "and have passed through dozens of replicative (reproductive) cycles," Gearhart says. "We feel that these things do have some replicative immortality. They are acting very much like the mouse counterparts."

"We feel that if you can establish a number of these (cell) lines, you wouldn't have to consistently go back to get more tissue." In terms of ethical implications, Gearhart sees two sides to such considerations -- germ line alterations and human cloning. He notes that in the mouse, germ lines have already been used to create genetically-altered animals for research. "Clearly, it would be totally unethical to do (in humans), and we wouldn't be involved with any of this kind of thing," he says. "But, when you get to the issue of cloning... I would anticipate that nuclei taken out of these types of cells would be ideal candidates to clone, to use as donor cells (for cloning)," Gearhart adds.

In terms of his own research prospects, the researcher says one of the types of studies he has in mind is to alter certain genes in these stem cells, "but targeted only at enhancing the likelihood of a graft (transplantation) not being rejected by a host." "Maybe we could reach the point where we could customize these cells such that they would have the same genes as a potential host," he says.

SOURCE: New Scientist (July 19, 1997, p. 4)

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