Human Embryonic Stem Cells May Promise Medical Advances

Transplantation medicine based on stem cells remains a distant hope for now, Science editors cautioned. But, the Science study describes intriguing early results:

For the first time, researchers have reported the development of versatile "pluripotent" human embryonic stem cells, potentially capable of becoming any cell in the body, from a cloned human blastocyst. The stem cells were harvested from a blastocyst produced by transferring the nucleus of a non-reproductive ("somatic") cell, containing a woman's genetic blueprint, into a nucleus-free egg from the same donor.

Following this transfer, factors within the host egg's exterior, or cytoplasm, reprogrammed its new nuclear contents by activating versatile embryonic genes, while silencing the more limited adult somatic cell genes. Researchers were then able to collect embryonic stem cells from the resulting cell mass inside the cloned blastocysts.

In theory: "Because these cells carry the nuclear genome of the individual, after differentiation they could be expected to be transplanted without immune rejection for treatment of degenerative disorders," reported Woo Suk Hwang of Seoul National University in Korea. "Our approach opens the door for the use of these specially developed cells in transplantation medicine."

Embryonic stem cells have previously been produced with cells from mice using the same method, called "somatic cell nuclear transfer." But, achieving this trick with human cells posed unique challenges, said Donald Kennedy, Science's Editor-in-Chief.

The researchers attribute their apparent success to the use of extremely fresh donor eggs, stringent timing protocols, and a special method for gently extruding rather than suctioning the DNA-spindle complex from eggs. Suctioning the DNA may damage spindles, possibly causing chromosomal defects called aneuploidy, they noted.

Hwang and colleagues developed the stem cell line, SCNT-hES-1, after collecting 242 eggs from 16 unpaid volunteers who had signed informed-consent agreements. From these eggs, scientists then cultured 30 blastocysts to obtain 20 suitable inner cell masses. By tweaking the amount of time that elapsed between the transfer of the nucleus and the activation of the newly transplanted genetic material, the team was able to optimize their results: A two-hour delay seemed to work best, so that 20 percent of all reconstructed eggs formed blastocysts. From the inner cell mass of these blastocysts, a single human embryonic stem cell line was obtained.

The resulting stem cells differentiated into all three of the main tissue types that appear at the beginning stages of development, researchers reported. When transplanted into mice, the stem cells differentiated into still more specific cell types, offering further proof of pluripotency.

Interestingly, the research team harvested eggs as well as somatic cells from the same donors: Nuclear material from the somatic cell was transferred into the nucleus-free or enucleated egg of the same woman. This unusual experimental design may be more effective than person-to-person transfers because it offered greater compatibility between the genetic components that were fused together.

But, were the stem cells truly derived from the transferred nucleus, or were they the result of an accidental "parthenote"--an artificially induced blastocyst resulting from an egg that began to spontaneously divide? To support their claim that the resulting stem cells came from the transplanted nucleus, Hwang's team completed DNA fingerprinting analysis, and also checked the expression of imprinted genes. The results were consistent with stem cells resulting from transplantation.

Many questions remain, Science's Donald Kennedy said: "The potential for embryonic stem cells is enormous, but researchers still must overcome significant scientific hurdles," Kennedy remarked. "These results seem promising. But, it's important to remember that cell and tissue transplantation and gene therapy are still emerging technologies, and it may be years yet before embryonic stem cells can be used in transplantation medicine."

The research also raises policy and ethical questions, Kennedy noted, since blastocyst-derived stem cells for tissue repair or transplantation might exacerbate pressures on egg donors in some regions. The prospect of using cloned human blastocysts to produce new embryonic stem cells lines also is likely to provoke further controversy, he added. "There is widespread consensus among all responsible, mainstream scientists--including the authors of this paper and AAAS, publisher of Science Magazine--that any attempt to clone a human being would be highly dangerous and wrong, and therefore, all reproductive cloning should be banned," Kennedy said. "But, the generation of stem cells by somatic cell nuclear transfer methods involving the same individuals may hold promise for advances in transplantation technology that could help people affected by many devastating conditions."

In addition to Hwang, authors on this Science paper were Young June Ryu, Eul Soon Park, Eu Gene Lee, Hyun Yong Chun, Byeong Chun Lee, Sung Keun Kang, Curie Ahn and Shin Yong Moon, all of Seoul National University; as well as Jong Hyuk Park and Sun Jong Kim of Mizmedi Hospital in Seoul; Ja Min Koo of Gachon Medical School; Jung Hye Hwang of Hanyang University; Ky Young Park of Sunchon National University; and Jose B. Cibelli of Michigan State University.

WWW: http://www.sciencemag.org/cgi/content/abstract/1094515

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MEDIA NOTE: A newsbriefing on this research will take place at 11:00 a.m. Pacific Time, Thursday, 12 February, during the AAAS Annual Meeting in Seattle, in the Eliza Amphitheater, Grand Hyatt. Further, these and other speakers will take part in a symposium titled, "Stem Cell Science in the Service of Society," at 2:30 p.m. Monday, 16 February, Sheraton Hotel, Second Floor, Grand Ballroom C. Press registration is in the AAAS Press Center in Leonesa I of the Grand Hyatt Hotel.

AAAS is the world's largest general scientific society, dedicated to "Advancing science · Serving society."

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