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QueerNews版 - UCLA-engineered stem cells seek out and kill HIV in living organisms
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话题: hiv话题: cells话题: ucla话题: engineered
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Expanding on previous research providing proof-of-principle that human stem
cells can be genetically engineered into HIV-fighting cells, a team of UCLA
researchers has now demonstrated that these cells can actually attack HIV-
infected cells in a living organism.
The study, published April 12 in the journal PLoS Pathogens, demonstrates
for the first time that engineering stem cells to form immune cells that
target HIV is effective in suppressing the virus in living tissues in an
animal model, said 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.
"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," he said.
In the previous research, the scientists took CD8 cytotoxic T lymphocytes —
the "killer" T cells that help fight infection — from an HIV-infected
individual and identified the molecule known as the T cell receptor, which
guides the T cell in recognizing and killing HIV-infected cells. However,
these T cells, while able to destroy HIV-infected cells, do not exist in
great enough quantities to clear the virus from the body. So the researchers
cloned the receptor and used this to genetically engineer human blood stem
cells. They then placed the engineered 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, multi
-functional HIV-specific CD8 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 this current study, the researchers similarly engineered human blood stem
cells and found that they can form mature T cells that can attack HIV in
tissues where the virus resides and replicates. They did so by using a
surrogate model, the humanized mouse, in which HIV infection closely
resembles the disease and its progression in humans.
In a series of tests on the mice's peripheral blood, plasma and organs
conducted two weeks and six weeks after introducing the engineered cells,
the researchers found that the number of CD4 "helper" T cells — which
become depleted as a result of HIV infection — increased, while levels of
HIV in the blood decreased. CD4 cells are white blood cells that are an
important component of the immune system, helping to fight off infections.
These results indicated that the engineered cells were capable of developing
and migrating to the organs to fight infection there.
The researchers did note a potential weakness with the study: Human immune
cells reconstituted at a lower level in the humanized mice than they would
in humans, and as a result, the mice's immune systems were mostly, though
not completely, reconstructed. Because of this, HIV may be slower to mutate
in the mice than in human hosts. So the use of multiple, engineered T cell
receptors may be one way to adjust for the higher potential for HIV mutation
in humans.
"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," Kitchen said.
The researchers will now begin making T cell receptors that target different
parts of HIV and that could be used in more genetically matched individuals
, he said.
Other study authors are Bernard R. Levin, Gregory Bristol, Valerie Rezek,
Sohn Kim, Christian Aguilera-Sandoval, Arumugam Balamurugan, Otto O. Yang
and Jerome A. Zack, all of UCLA.
The National Institutes of Health, the California HIV/AIDS Research Program,
the California Institute for Regenerative Medicine, the UC Multicampus
Research Program and Initiatives from the California Center for Antiviral
Drug Discovery, and the UCLA Center for AIDS Research (CFAR) funded this
study.
The UCLA AIDS Institute, established in 1992, is a multidisciplinary think
tank drawing on the skills of top-flight researchers in the worldwide fight
against HIV and AIDS, the first cases of which were reported in 1981 by UCLA
physicians. Institute members include researchers in virology and
immunology, genetics, cancer, neurology, ophthalmology, epidemiology, social
sciences, public health, nursing and disease prevention. Their findings
have led to advances in treating HIV, as well as other diseases, such as
hepatitis B and C, influenza and cancer.
For more news, visit the UCLA Newsroom and follow us on Twitter.
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相关话题的讨论汇总
话题: hiv话题: cells话题: ucla话题: engineered