Stem cell transplant problem solved, UCSD-led study says

Posted: January 3, 2014 at 6:42 am

(This is my blog post about the embryonic stem cell study. For my news article about the study, go here.)

Genetically modified human embryonic stem cells can solve 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 modifying them to make two immune-suppressing chemicals, according to a study performed in mice given a human immune system. Immune functioning in the rest of the animal remains active. The immune protection also applies to differentiated cells derived from the stem cells.

If the approach works in people, patients receiving transplanted tissue or organs made from embryonic stem cells wouldn't have to take harsh immune-suppressing drugs, said Yang Xu, a UCSD professor of biology. The method also may prevent immune rejection of tissues grown from other types of stem cells.

These arehumanized laboratory mice that contain a functional human immune system. Such mice have been used for years; a UCSD research team developed a model with a stronger immune response to test their immune-suppressing tissues. / Zhili Rong, UCSD

Researchers placed genes in the stem cells to produce the two chemicals, CTLA4-lg and PD-L1, naturally made in the body. The humanized immune systems of the mice accepted transplants of cells engineered to make the chemicals. The researchers transplanted cardiomyocytes and fibroblasts derived from the engineered stem cells. Transplants derived from regular embryonic stem cells were rejected.

The study was published online Thursday in the journal Cell Stem Cell. Its findings will have to be confirmed for safety and effectiveness in more animal studies before human trials can be considered, which will take years. The mouse model itself was "optimized" for the study to more faithfully reflect the human immune system than other immune models, the study said.

Xu said a further study is being considered in monkeys, a large animal model considered to better reflect human biology than mice.

Embryonic stem cells are being tested along with many other kinds of stem cells to replace diseased or destroyed body parts, such as spinal cord segments and insulin-producing beta cells in the pancreas. All of these cells have advantages and drawbacks. Immune rejection, along with a tendency to form tumors, are two big drawbacks to embryonic stem cells.

San Diego-based ViaCyte is preparing to test a therapy with beta cells within a year. The company encapsulates them in a permeable barrier that allows insulin to diffuse out but prevents the immune system from entering. However, that approach won't worth with transplants that must integrate into the body, such as spinal cord tissue. So a way of turning off the immune system just in those cells is an attractive idea.

Read more here:
Stem cell transplant problem solved, UCSD-led study says

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