New way of overcoming human stem cell rejection discovered

Biologists have discovered an effective strategy that could prevent the human immune system from rejecting the grafts derived from human embryonic stem cells, a major problem now limiting the development of human stem cell therapies.

The discovery by UC San Diego researchers may also provide scientists with a better understanding of how tumors evade the human immune system when they spread throughout the body.

The study by a collaboration that included scientists from China, was enabled by the development of "humanized" laboratory mice that contained a functional human immune system capable of mounting a vigorous immune rejection of foreign cells derived from human embryonic stem cells.

Because human embryonic stem cells are different from our own body's cells, or "allogenic," a normally functioning human immune system will attack these foreign cells. One way to reduce the body's "allogenic immune response" is to suppress the immune system with immunosuppressant drugs.

The biologists took immune deficient laboratory mice and grafted into their bodies human fetal thymus tissues and hematopoietic stem cells derived from fetal liver of the same human donor. "That reconstituted in these mice a normally functioning human immune system that effectively rejects cells derived human embryonic stem cells," Yang Xu, who headed the team of researchers, said.
With these "humanized" mouse models, the biologists then tested a variety of immune suppressing molecules alone or in combination and discovered one combination that worked perfectly to protect cells derived from human embryonic stem cells from immune rejection.

That combination was CTLA4-lg, an FDA-approved drug for treating rheumatoid arthritis that suppresses T-cells responsible for immune rejection, and a protein called PD-L1 known to be important for inducing immune tolerance in tumors.

The researchers discovered that the combination of these two molecules allowed the allogeneic cells to survive in humanized mice without triggering an immune rejection.

The study was published in the journal Cell Stem Cell.

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Bulletproof Vests from Stem Cells?

In a breakthrough, Cambridge scientists have discovered a bizarre new property in the nuclei of embryonic stem cells that could pave the way for gen-next bulletproof vests. Stem cells - the body's master cells - demonstrate the property never before seen at a cellular level, scientists said.

The property - known as auxeticity - is one which may have application as wide ranging as soundproofing, super-absorbent sponges and bulletproof vests, they said. Most materials when stretched will contract. The opposite is also true: squeeze a material and it will expand.

However, scientists have begun to explore auxeticity, an unusual property which has the opposite effect - squeeze it and it will contract, stretch it and it will expand. This means that auxetic materials act as excellent shock absorbers or sponges, a fact that is being explored for various uses.

Until now, auxeticity has only been demonstrated in man-made materials and very rarely in nature, such as some species of sponge. Ateam of University of Cambridge researchers observed auxeticity in the nuclei of embryonic stem cells, master cells within the body which can turn into any other type of cell.

"This is a pretty bizarre finding and very unexpected. When the stem cell is in the process of transforming into a particular type of cell, its nucleus takes on an auxetic property, allowing it to 'sponge up' essential materials from its surrounding," Kevin Chalut from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, who led the study, said.

"This property has not, to my knowledge, been seen before at a cellular level and is highly unusual in the natural world," Chalut said. The auxetic properties only appear in the stem cell's nucleus when it is in the transition stage, changing from an embryonic, non-specific stem cell into a differentiated, tissue-specific cell, such as a heart tissue cell. The research was published in the journal Nature Materials.

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