One of the toughest problems facing embryonic stem cell therapy, immune rejection of transplanted cells, may have been solved, according to a UC San Diego-led research team.

The cells can be made invisible to the immune system by genetically engineering them to make two immune-suppressing molecules, according to the study. Researchers tested the approach in mice given a human immune system. Immune functioning in the rest of the animal remained active.

If the approach works in people, patients receiving transplanted tissue or organs made from embryonic stem cells wouldnt have to take harsh immune-suppressing drugs, said study leader Yang Xu, a UC San Diego professor of biology.

Human embryonic stem cells. The green markers indicate the presence of a protein expressed only in these cells. / Samantha Zeitlin, 2006 CIRM fellow

Researchers placed genes in the stem cells to produce the two molecules, called CTLA4-lg and PD-L1, naturally made in the body. The mice accepted transplants of heart and skin cells derived from the engineered stem cells. They rejected transplants derived from regular embryonic stem cells.

The study was published online Thursday in the journal Cell Stem Cell. Its findings will have to be confirmed for safety and effectiveness before human trials can be considered, which will take years.

Three scientists given the paper for comment had mixed reactions. While they praised the works scientific prowess, two said genetically engineering the transplanted cells could cause serious side effects that might preclude their use.

The researchers employed a clever strategy to use the immune systems natural regulatory systems, said Mitchell Kronenberg, president of the La Jolla Institute for Allergy & Immunology.

This is an especially promising approach, because it avoids the toxic side effects of the drugs now used to suppress the rejection response, and therefore this is an important step forward in showing the feasibility of using human embryonic stem cells from unrelated donors, Kronenberg said.

More skeptical were Jeanne Loring, a stem cell researcher at The Scripps Research Institute, and Craig M. Walsh, associate director of the Institute for Immunology at UC Irvine.

Link:
Embryonic stem cell rejection problem fixed, study says

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