December 3, 2007

Versatile Human Stem Cells Created Without Embryos

Cell culture flasks used to propagate stem cells Cell culture flasks used to propagate stem cells.Wellcome Library, London

Two separate research teams have figured out how to "reprogram" cells with just a handful of genes to give them the characteristics of embryonic stem cells. The breakthrough may eventually put to rest the ethical controversy surrounding stem cells.

Researchers have been hoping to harness the therapeutic potential of cloning ever since the cloning of Dolly the sheep in 1997. Cloning entails taking the nucleus — the compartment that contains the DNA — from an adult cell and putting it into an egg from which the original nucleus has been removed. The egg then "reprograms" the adult nucleus so that the cell behaves like an embryo but has the genes of the adult cell.

When an embryo like this is implanted into a uterus, as with Dolly, the process is called reproductive cloning. In another strategy, called therapeutic cloning, the embryo can instead be used to create stem cells that are genetically identical to a patient. Since embryonic stem cells have the ability to form virtually any cell type in the body, those taken from a cloned embryo could potentially be used to treat many diseases. Therapeutic cloning has garnered a great deal of attention over the past few years, but until now it had only been achieved in the mouse.

Researchers reported in Nature on November 22, 2007, that they successfully isolated 2 embryonic stem cell lines from cloned embryos made using cells from the skin of an adult rhesus macaque. Before this new study was published, Nature asked another group of researchers to confirm that the stem cells were genetically identical to the donor skin cells. Their report, published in the same issue of the journal, confirms that therapeutic cloning has now been accomplished in primates for the first time.

The team that isolated the embryonic stem cell lines was led by Dr. Shoukhrat Mitalipov at Oregon Health and Science University in Portland. Their work was supported by NIH's National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Child Health and Human Development (NICHD) and National Center for Research Resources (NCRR).

The stem cells, the researchers showed, could turn into heart or nerve cells in the laboratory, and had other characteristics of established embryonic stem cell lines. One of the keys to the research team's success was that they used a newer, more precise technique for removing the egg's genetic material.

Although this study proves that the therapeutic cloning of primates is possible, there are still many hurdles to be overcome. In particular, the efficiency of the process will have to be improved before the technique could be applied in the clinic using human cells. The team injected 314 eggs to get the 2 stem cell lines — an efficiency of less than 1%.

— by Harrison Wein, Ph.D.

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