A promising type of stem cell may not be as well-suited for tissue replacement transplants as scientists had hoped. According to new research published in Nature, induced pluripotent stem (iPS) cells—which are derived from adult tissue but, like embryonic stem cells, have the potential to proliferate indefinitely and to turn into any type of tissue—trigger an immune reaction when the undifferentiated cells are transplanted into tissue-matched mice.

However, the significance of the finding is not yet clear. Researchers have only studied cells from mice, and human iPS cells may not trigger the same reaction. In addition, most stem cell-based therapies would involve transplantation of differentiated cells, such as brain cells or liver cells, which might not provoke the immune system.

IPS cells, first derived in 2007, elicited excitement among the regenerative medicine field because they could theoretically be made from skin cells from any patient, generating genetically matched cells that would presumably not trigger an immune reaction. (Cell transplants from a non-matched donor require the recipient take immune-suppressing drugs.)

Researchers from the University of California, San Diego, tested the theory by creating both embryonic stem cells and iPS cells from mice and then transplanting the cells into genetically identical mice. The animals' immune system attacked the iPS cells but not the embryonic stem cells.

According to an article in Nature;

When transplanted, the embryonic stem cells gave rise to teratomas — tumours containing a chaotic jumble of cell types, which are used as a signifier of a cell's pluripotency. Most of the iPS cells, by contrast, were not able to form teratomas, or made teratomas that were attacked or rejected by the immune systems of the host mice.

... The team found that certain genes were expressed at much higher levels in the teratomas formed by iPS cells than in those formed by embryonic stem cells. Two of the genes — Zg16 and Hormad1 — were specifically targeted in immune attacks. Xu suggests that these genes are normally turned off by the time a fetus begins the process of developing immune tolerance to its own tissues, so they are not recognized as 'self' by the host's body; the iPS reprogramming procedure might alter the normal expression of these genes.

IPS cells are currently being used to screen drugs and study disease; scientists have developed cell lines from people with different disorders, such as Parkinson's. They then differentiate the cells into the cell type damaged in the disease and search for the underlying molecular flaws. Researchers emphasize that iPS cells still relatively little studied compared to embryonic stem cells, and extesnvie research is needed before using them in therapies. Another recent study, for example, showed that iPS cells seem to have more genetic abnormalities than embryonic stem cells.

Stem cells genetically engineered to carry a molecule (derived from an HIV-infected person) that recognizes the virus could provide a new way to bolster the immune system against the disease, according to new research published this week in PLoS ONE. When implanted into mice, the stem cells developed into mature immune cells that could target cells with HIV specific proteins. Researchers are using a similar approach to prime the human immune system against cancer.

"We have demonstrated in this proof-of-principle study that this type of approach can be used to engineer the human immune system, particularly the T-cell response, to specifically target HIV-infected cells," says lead investigator Scott G. Kitchen, an assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute, in a press release. "These studies lay the foundation for further therapeutic development that involves restoring damaged or defective immune responses toward a variety of viruses that cause chronic disease, or even different types of tumors."

According to the release:

Taking CD8 cytotoxic T lymphocytes--the "killer" T cells that help fight infection--from an HIV-infected individual, the researchers identified the molecule known as the T-cell receptor, which guides the T cell in recognizing and killing HIV-infected cells. These cells, while able to destroy HIV-infected cells, do not exist in enough quantities to clear the virus from the body. So the researchers cloned the receptor and genetically engineered human blood stem cells, then placed the stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.

The engineered stem cells developed into a large population of mature, multifunctional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also found that HIV-specific T-cell receptors have to be matched to an individual in much the same way that an organ is matched to a transplant patient.

Researchers hope the technology will have broader applications."This approach could be used to combat a variety of chronic viral diseases," says co-author Jerome A. Zack, a UCLA professor of medicine in the division of hematology and oncology and associate director of the UCLA AIDS Institute, in the same release. "It's like a genetic vaccine."