Embryonic Stem Cell Success
Saturday, March 25, 2006
Scientists in Germany said yesterday that they had retrieved easily obtained cells from the testes of male mice and transformed them into what appear to be embryonic stem cells, the versatile and medically promising biological building blocks that can morph into all kinds of living tissues.
If similar starter cells exist in the testes of men, as several scientists yesterday said they now believe is likely, then it may not be difficult for scientists to cultivate them in laboratory dishes, grow them into new tissues and transplant those tissues into the ailing organs of men who donated the cells.
The technique would have vast advantages over the current approach to growing "personalized" replacement parts -- an approach that has stirred intense political controversy because it requires the creation and destruction of cloned human embryos as stem cell sources. The new work suggests that every male may already have everything he needs to regenerate new tissues -- at least with a little help from his local cell biologist.
No one knows whether cells with similar potential exist inside female bodies -- a crucial question if women, too, are to have access to new tissues genetically matched to themselves and so not susceptible to rejection by their immune systems. But recent studies have led many researchers to conclude that the possibility is greater than previously believed.
"We may not be as successful in getting the same result in humans as in mice," said study leader Gerd Hasenfuss, a cardiologist at Georg-August-University of Goettingen. "But I am very much convinced that this is the basis for a therapeutic strategy. I am optimistic."
Other scientists said the findings are exciting but reiterated Hasenfuss's first point, noting that mice have been cured of many diseases that still kill humans every day.
"The major caveat is that this was done in mice, and unfortunately we're starting to learn there really is a difference between mouse and human," said Evan Snyder, director of the stem cell program at the Burnham Institute in San Diego.
Embryonic stem cells are among the earliest cells to appear in newly developing organisms and have the potential to become every kind of cell or tissue in the body. In recent years, scientists have learned to keep them alive in laboratory dishes and, by adding certain nutrients or hormones, coax them to become pancreatic cells, cardiac cells, nerve cells or others that may someday serve as living "patches" for patients with diabetes, heart disease, spinal cord injuries or other degenerative conditions.
The new report, published yesterday in the online edition of the journal Nature, is not the first claimed discovery of an alternative source of embryonic stem cells. But previous claims, including the purported discovery of such cells in everything from menstrual blood to bone marrow to fat, have suffered from incomplete evidence for their biological versatility, or have proved to be too rare or difficult to isolate to be of practical value.
By contrast, the new work involves cells that were numerous and easy to find; if they exist in men, Hasenfuss said, they could probably be obtained with biopsy techniques routinely used in male fertility studies. And the cells passed every gold-standard test used today to prove their equivalence to embryonic stem cells.
"The evidence presented looks very good indeed, and we should welcome this new advance in stem cell research and the possibilities that it opens up," said Allan Spradling, a Howard Hughes Medical Institute investigator who studies early development at the Carnegie Institution of Washington.
Hasenfuss, with study co-leaders Wolfgang Engel and Kaomei Guan, isolated from mouse testes "spermatogonial stem cells," which are the mother cells that give rise to a steady supply of sperm throughout a male's life. They showed that under carefully controlled conditions, those cells can become "multipotent adult germline stem cells" that share all the characteristics of embryonic stem cells.
They can make countless copies of themselves, for example, and under the right conditions will morph into any kind of body cell. Among others, Hasenfuss has already grown liver cells, muscle cells, pancreas cells, dopamine-secreting nerve cells (the kind that die off in Parkinson's disease) and various kinds of heart cells, which spontaneously coalesced in a lab dish and started beating in synchrony.
German scientists have great incentive to find alternatives to human embryonic stem cells, because government restrictions on human embryo cell research in Germany are even more severe than they are in the United States, where federally funded scientists are banned from working on embryonic stem cell colonies created after August 2001.
Still, Hasenfuss said he favors scientists' being allowed to pursue both embryonic cells and alternatives until it is clear which avenue shows the most medical promise.
As an aside, he noted that the editors at Nature demanded many additional tests and an unusually thick pile of documentation before accepting his report for publication -- a result, he said, of the embarrassment that its sister journal, Science, recently faced when seemingly monumental stem cell studies by Korean researcher Hwang Woo Suk proved to have been faked.
Rudi Jaenisch, a stem cell researcher at the Whitehead Institute for Biomedical Research in Cambridge, Mass., said he found the new report "pretty convincing" but warned that further studies would be needed to show that the cells remain normal over time. His main concern is that sperm-producing cells often bear molecular "imprints" that can interfere with their ability to produce normal tissues.
Hasenfuss said that he had not tested for those imprints yet but that the tissues so far appear normal.
Until recently, it was thought that girls are born with all the egg cells they will ever have, which would suggest that female equivalents of Hasenfuss's testicular cells don't exist. But a Harvard team last year found evidence of egg production in adult mice, suggesting that egg precursor cells similar to Hasenfuss's sperm-producing cells may be housed in women's ovaries. If so, Hasenfuss said, they too may be able to become embryonic stem cells.