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Stem Cells Seek and Kill HIV in Living Organisms

In a study published April 12 in the journal PLoS Pathogens, the scientists demonstrated for the first time that engineering stem cells to form immune cells targeting HIV is effective in suppressing the virus in living tissues in an animal model.

Lead investigator Scott G. Kitchen, an assistant professor of medicine at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute, commented, "We believe that this study lays the groundwork for the potential use of this type of an approach in combating HIV infection in infected individuals, in hopes of eradicating the virus from the body."

The study expanded on previous research by the team in which they were able to engineer stem cells that could specifically target cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.

In the current study, the researchers similarly engineered human blood stem cells and found that they can form mature T cells that attack HIV in tissues where the virus resides and replicates. They did so by using a mouse model in which HIV infection closely resembles the disease and its progression in humans.

In a series of tests conducted two weeks and six weeks after introducing the engineered cells to the mice, the researchers found that the number of CD4 "helper" T cells — the infection fighting white blood cells that are depleted as a result of HIV infection — increased, while levels of HIV in the blood decreased. These results indicated that the engineered cells were capable of developing and migrating to the organs to fight infection there.

The researchers noted that multiple engineered T cell receptors could be needed to adjust for the higher potential for HIV mutation in humans, as HIV may be slower to mutate in the mice models than in humans. Still, they believe it is a 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. They will now begin making T cell receptors that target different parts of HIV and that could be used in more genetically matched individuals, Kitchen said.

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