South Korean researchers have created 11 new lines of human embryonic stem cells that for the first time are genetically matched to diseased or disabled patients. Woo Suk Hwang, DVM, PhD, of the College of Veterinary Medicine, Seoul National University, and colleagues are hopeful that the patient-specific, immune-matched human embryonic stem cells will be of great importance for studies of disease and development and for advancing clinical deliberations for stem cell transplantation. The new stem cells come one year after the same group of investigators derived a single cell line from a cloned human embryo.

The researchers, who published their findings on the May 19 Sciencexpress Web site, detailed how the new cells were established via nuclear transfer of skin cells from patients with disease or injury into donated oocytes. The cell lines, which were grown on human feeders from the same nuclear transfer donor or genetically unrelated individuals, were established at high rates, regardless of the sex or age of the nuclear transfer donor, according to Dr. Hwang. The stem cells were pluripotent and chromosomally normal, and they matched nuclear transfer patients’ DNA. The technique may allow researchers to overcome the difficulty created by the body’s own immune system, which often rejects transplants.

“The work in this study shows that stem cell lines can be generated using somatic cells from patients with disease and injury,” Dr. Hwang reported. “It may also be possible to generate nuclear transfer human embryonic stem cell lines from patients with diseases and disorders of unknown causes. For example, nuclear transfer human embryonic stem cells derived from early onset Alzheimer’s disease or autism patients might prove invaluable for mechanistic studies in vitro after differentiation into neuroprogenitors.”

“It’s a breakthrough that I didn’t think would happen for decades,” reported Gerald Schatten, PhD, Professor of Research Development at the University of Pittsburgh School of Medicine and coauthor of the report.

PATIENT-SPECIFIC STEM CELLS

Patients in the study had either a genetic immunodeficiency disease, (congenital hypogammaglobulinemia), disorders caused by injury (spinal cord injury), or other conditions caused by complex autoimmune mechanisms (juvenile diabetes). The patients (eight males) ranged in age from 2 to 56. A total of 185 oocytes were donated by 18 women; 125 of the oocytes were provided by 10 women younger than 30. Ultimately, 11 new nuclear transfer human embryonic stem cell lines were established from 31 nuclear transfer blastocysts.

The single cell line produced last year resulted from nuclear transfer in which the oocyte and somatic cell came from the same healthy female. That work generated one cell line from more than 200 attempts. However, this time the researchers improved the efficiency of the process, consistently deriving a cell line in fewer than 20 tries.

It may be years before stem cell therapy’s full potential can be used in humans, and the researchers noted a number of issues that must be addressed. First, the stem cell lines produced from patients with disease will likely display characteristics of the disease, so they will probably not be appropriate for direct use in treating patients. In addition, researchers must develop methods to efficiently direct the differentiation of embryonic stem cells to specific stable cell types, as well as find a way to remove the remaining animal components from the laboratory procedures. Currently, the procedure for isolating nonreproductive cells for the nuclear transfer method involves animal enzymes and serum.

ETHICAL DEBATE

Dr. Hwang’s group’s findings will likely fuel the ongoing debate regarding the ethics of so-called therapeutic cloning. In the same issue of Sciencexpress, researchers David Magnus and Mildred K. Cho, from the Stanford Center for Biomedical Ethics and Department of Pediatrics at Stanford University in Palo Alto, California, expressed their own concerns. “This work raises ethical and policy questions for human embryonic stem cell researchers,” they reported. “As human embryonic stem cell research proceeds internationally, these issues must be adequately addressed for public confidence to be maintained.... Their work is in such a novel and controversial area that it is unsurprising that it raises new ethical challenges, and is beset by some ambiguities. To facilitate the scientific and ethical dialog around frontier research, journals are obligated to publish such research and to encourage ethical reflection on how future research should be conducted.”

The findings by the South Korean researchers will also add to the political debate regarding funding for embryonic stem cell research in the United States. In May, the US House of Representatives passed a bill that would expand public funding for embryonic stem cell research. However, President Bush has threatened to veto it, saying that he opposes the use of federal money to “promote science which destroys life in order to save life.” The vote came up short of the two-thirds supermajority needed to override such a veto. The House also passed a proposal that would use federal money to study stem cells that are taken from adults and umbilical cord blood, instead of human embryos. In 2001, President Bush had previously limited funding for research on human embryonic stem cells to those cell lines that were already in existence at the time.

NR

—Colby Stong

Suggested Reading
Hwang WS, Roh SI, Lee BC, et al. Patient-specific embryonic stem cells derived from human SCNT blastocysts. Available at: www.sciencemag.org/sciencexpress/recent.shtml. Accessed May 19, 2005.
Hwang WS, Ryu YJ, Park JH, et al. Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst. Science. 2004;303:1669-1674.
Magnus D, Cho MK. Issues in oocyte donation for stem cell research. Available at: www.sciencemag.org/sciencexpress/recent.shtml. Accessed May 19, 2005.

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