In a setback for a promising kind of therapy based on artificial embryonic stem cells, a study published Wednesday in the journal Nature has found that they have serious quality issues.

Scientists who conducted the study, including those from the Salk Institute and UC San Diego in La Jolla, said it should be possible to improve the quality of these cells, which are called induced pluripotent stem cells. They said lessons can be learned from a technique of making embryonic stem cells through nuclear transfer, the same technology used to create Dolly the cloned sheep.

In addition, the study does not prove that the quality problems will actually affect the envisioned therapy, said scientists who examined it. That remains to be tested.

Induced pluripotent stem cells, called IPS cells for short, are made from skin cells treated with reprogramming factors that turn back the clock so they very closely resemble embryonic stem cells. The hope is that IPS cells could be turned into cells that can repair injuries or relieve diseases. Because they can be made from a patients own cells, IPS cells are genetically matched, reducing worries of rejection by a persons immune system.

In San Diego, scientists led by Jeanne Loring at The Scripps Research Institute have created IPS cells from the extracted skin cells of Parkinsons disease patients and turned those IPS cells into neurons that produce dopamine. They hope to get federal approval next year to implant the customized cells back into the patients and see whether the treatment is effective.

A major concern is that IPS cells display abnormal patterns of gene activation and repression. This is controlled by a process called methylation, which adds molecules called methyl groups to DNA. Methylation represses genes, while removing the methyl groups, or demethylation, activates them.

The Nature study was led by Shoukhrat Mitalipov of Oregon Health & Science University. Mitalipov made headlines last year for using nuclear transfer to derive human embryonic stem cells, the first time this has been achieved. Cells produced through this method can form a near-perfect genetic match to the patient, and their quality closely resembles those of true embryonic stem cells.

We know that the embryonic stem cells are the gold standard, and weve been always trying to make patient-matched cells that would match the gold standard, Mitalipov said. And at this point, it looks like the (nuclear transfer) cells produce exactly those cells that would be best.

Nuclear transfer involves placing a nucleus from a skin cell into an egg cell that has had its nucleus removed. The cell is then stimulated, and it starts dividing in the same way a fertilized egg cell divides to form an embryo.

The new study found that when compared with the IPS cell method, nuclear transfer yields stem cells that much more closely resemble natural embryonic stem cells.

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