Updated 21 January 2005: Science magazine has formally retracted this paper because its data were fabricated; see ARF related news story.
In February 2004, researchers at Seoul National University in Korea surprised the world when they reported that they had isolated the first human clone by somatic cell nuclear transfer (see ARF related news story). That technique, commonly called therapeutic cloning, led to the development of a human blastocyst from which Woo Suk Hwang and colleagues were able to extract human embryonic stem cells. The paper was a milestone, but it also raised an interesting question. To get the blastocyst, Hwang and colleagues had taken nuclei from somatic cells, the cumulus cells that surround oocytes in the ovary, and injected them into enucleated oocytes from the same donor. Could the embryo actually have been derived by parthenogenesis, the rare but documented development of an unfertilized egg into an embryo (see ARF related news story on primate parthenogenesis). In today’s Sciencexpress, Hwang, Gerald Schatten, and colleagues in Korea and at the University of Pittsburgh School of Medicine, Pennsylvania, would seem to put such questions to rest. They report that they have repeated the procedure—11 times—using nuclei and oocytes from different donors.
Today’s paper is sure to be another milestone for many reasons. Not only does it confirm that therapeutic cloning is possible in humans, but it also suggests that the procedure is a relatively easy way to develop patient-specific embryonic stem cells. What’s more, the researchers devised a way to grow those embryonic stem cells on human feeder cells; most human embryonic cell lines isolated to date have been grown on mouse feeder cells, making them unsuitable for use in human experiments.
Hwang and colleagues used somatic cell nuclear transfer (SCNT) to plant skin nuclei from patients suffering from injury or disease into enucleated oocytes isolated from healthy female donors. In most cases, the nuclei and oocytes were from unrelated volunteers. The authors successfully fused nuclei in 129 out of 185 attempts. Thirty-one (24 percent) went on to form blastocysts and from these Hwang and colleagues generated 11 embryonic stem cell lines. The nuclei donors (10) ranged from 2 to 56 years old, and were suffering from spinal cord injury, juvenile diabetes, or congenital hypogamma-globulinemia, an immunodeficiency disorder.
The stem cells had the chromosomal karyotype of the donor (male for male donors, female for female) and the authors used DNA fingerprinting to confirm that the cell lines were derived from the correct nuclei donor. The stem cells expressed markers common to pluripotent stem cells and each was capable of generating into cells of all three germ layers: ectoderm, mesoderm, and endoderm.
As the authors write, “these cells are still likely to be defective and cannot be used directly in cell transplantation to patients.” But they can be used to study disease progression and assist in drug development. The study also opens up the possibility of generating patient-specific stem cells to generate tissue for repair in the case of a traumatic injury, such as spinal cord damage.
“This is a landmark paper that establishes the feasibility of generating embryonic stem cell lines from individuals with devastating diseases, including Alzheimer’s,” said David Scadden, professor of medicine at Harvard Medical School and co-director of the Harvard Stem Cell Institute. “The impact of this on developing therapies is still unknown, but at least now we can envision generating neurons in the laboratory that are genetically identical to those that are defective in people with the disease. That should mean we can study patients in great detail, evaluating them for why and how they are susceptible to disease, and whether specific modifications can alter their susceptibility to disease and screen compounds in hopes that some will become drugs to combat the disease. The much improved efficiency of successful nuclear transfer demonstrated by this paper also greatly reduces concerns about whether this process will ever be useful scientifically and mitigates concerns about needing so many donors that exploitation might become prevalent,” he added.
Federal funding cannot be used to conduct such research in the United States under current administration guidelines, prompting many US research institutions and states to seek private funding for stem cell research. But stem cell technology is shrouded in broader ethical debates, not only about whether therapeutic cloning should be legal or illegal, but also about how such research should be conducted. For example, ovarian hyperstimulation, which is necessary to harvest the oocytes needed for these experiments, is not without risk and can, in rare cases, leave donors infertile. In another article in today’s Sciencexpress, David Magnus and Mildred Cho, of the Stanford Center for Biomedical Ethics address this and other ethical issues that are sure to be increasingly relevant to all members of the research community now that the technical barriers to therapeutic cloning are falling.—Tom Fagan
No Available Further Reading
- Magnus D, Cho MK. Ethics. Issues in oocyte donation for stem cell research. Science. 2005 Jun 17;308(5729):1747-8. PubMed.
- Hwang WS, Roh SI, Lee BC, Kang SK, Kwon DK, Kim S, Kim SJ, Park SW, Kwon HS, Lee CK, Lee JB, Kim JM, Ahn C, Paek SH, Chang SS, Koo JJ, Yoon HS, Hwang JH, Hwang YY, Park YS, Oh SK, Kim HS, Park JH, Moon SY, Schatten G. Patient-specific embryonic stem cells derived from human SCNT blastocysts. Science. 2005 Jun 17;308(5729):1777-83. PubMed.