Gene Defect Corrected in Human Stem Cells

New research outlines a path toward new therapies with induced pluripotent stem cells.

For the first time, researchers have fixed the gene defect in cells from patients with an inherited disease, and then transformed the tissue into stem cells with the potential to reverse their condition. While scientists haven't yet tested the treatment in humans, the research could mark the beginning of a new age of curative treatments for many genetic disorders.

Correcting cells: Scientists corrected the genetic deficits in cells from patients with Fanconi anemia and then reprogrammed them into induced pluripotent stem cells. The cells can then be coaxed to differentiate into red blood cells. (Colonies of blood cells are shown at the bottom of the image.) Credit: Juan Carlos Izpisua Belmonte

The proof of concept study, led by Juan Carlos Izpisua Belmonte at the Salk Institute for Biological Studies, in La Jolla, CA, focused on patients with a rare condition, Fanconi anemia, which causes skeletal problems and bone-marrow failure, and raises sufferers' risk of cancer.

Researchers took skin cells from six patients and used a virus to deliver a functional copy of one of the faulty genes responsible for the condition. The method had previously been shown to correct the gene defect in mice.

Next, researchers used cell programming techniques that have emerged in the past two years to transform the cells into stem cells capable of growing into any tissue type--including the healthy blood cells needed to correct the patients' inherited anemia. Known as induced pluripotent stem cell (iPS) reprogramming, this involves introducing four genes known to be active in the developing embryo, which in turn change the cells' pattern of gene expression to one that resembles an embryonic cell rather than an adult one.

"Our work demonstrates that it is possible to combine gene and cell therapy using iPS technology to generate disease-free cells," says Belmonte. The research was published online in the journal Natureon Sunday.

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IPS cells are a particularly attractive medical tool for two key reasons. Unlike embryonic stem cells, iPS cells avoid the ethical controversy associated with harvesting human embryos. And because they come from the patient's own body, they will not be rejected by the immune system.

To test the therapy, scientists would need to grow blood progenitor cells from the genetically corrected iPS cells, and then transplant them back into patients, generating a supply of healthy blood cells. Belmonte notes, however, that the iPS cells that his team generated in the course of the study were not suitable for clinical use.