Researchers Combat HIV with Engineered Stem Cells

Horizons in Hemophilia, June 2012

Submitted by the National Hemophilia Foundation

A study published last month suggests that researchers at the University of California Los Angeles (UCLA) may have found a way to enlist genetically engineered human blood stem cells in the fight against HIV. Stem cells are unspecialized cells that can renew themselves for prolonged periods. They can also develop into many different cell types, making them a potentially renewable source of replacement cells to treat many conditions. The lead investigator of the study was Scott G. Kitchen, PhD, an assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA. He is a member of the UCLA AIDS Institute.

While earlier research has already demonstrated that CD8 cytotoxic T lymphocytes, or T cells, can kill HIV-infected cells, there are usually not enough of them to rid the body of the virus. The UCLA team focused on the T cell receptor, a molecule that helps the T cell identify and target HIV-infected cells. Kitchen and his colleagues then cloned the receptor and incorporated it into the development of genetically engineered human blood stem cells. The newly created stem cells were then placed into human thymus tissue that had been implanted in mice, allowing the investigators to study the reaction in a living organism. The thymus was chosen because it processes immune system T cells. So-called “humanized” mice models were used because they closely resemble the way HIV manifests itself in humans.

The researchers reported that the stem cells developed into a large group of mature, multifunctional T cells that could target and destroy cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to individuals, similar to the way organ matching is done for transplant patients.

Kitchen and his team then tested the mice’s blood, plasma and organs two weeks and six weeks after introducing the stem cells. They found that the number of CD4 “helper” T cells (white blood cells that combat infections), usually depleted from HIV infection, had increased and HIV levels in the blood had decreased. This confirmed that the engineered cells could develop and migrate to the sites where they were needed to fight infection. However, the investigators acknowledge that HIV may mutate more slowly in mice than humans and more research is needed.

“We believe that this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people,” concluded Kitchen. His team will now begin developing T cell receptors that target different parts of HIV, which could be used in people with the correct genetic match.

The study, “In Vivo Suppression of HIV by Antigen Specific T Cells Derived from Engineered Hematopoietic Stem Cells,” was published April 12, 2012, in the journal PLoS Pathogens.

Source: ScienceDaily, April 12, 2012