13 April 2012

Modified stem cells to fight HIV

Researchers from the University of California, working under the guidance of Associate Professor Scott G. Kitchen, have demonstrated the ability of specially modified human stem cells to turn into immune cells that effectively suppress the vital activity of HIV in an animal model.

As part of earlier work, scientists isolated HIV-specific cytotoxic CD8 T lymphocytes from the blood of HIV-infected patients and identified a molecule known as a T-cell receptor that ensures the destruction of infected cells by recognizing the HIV–1 Gag antigen protein. Unfortunately, the number of such cells in the human body does not allow you to completely get rid of the virus. Therefore, the researchers cloned the gene of this receptor and used it to create genetically modified human hematopoietic stem cells. These cells were injected into the human thymus tissue implanted in mice (the thymus gland, which plays an important role in the immune system), after which the behavior of the modified cells in a living organism was observed.

The cells differentiated and formed a large population of mature multifunctional CD8 T lymphocytes selectively destroying cells expressing HIV proteins.

In the latest work, the researchers injected similarly modified cells into so-called "humanized" mice. To create this model, animals are injected with suspensions of specially treated liver and thymus cells of the human fetus, as well as, after preliminary destruction of their own bone marrow with the help of radioactive irradiation, hematopoietic stem cells of the human fetus. The progression of HIV infection in such animals is almost similar to what happens in the body of an infected person.

The results of a series of analyses of peripheral blood, plasma and organ tissues of HIV-infected mice, conducted two and six weeks after the introduction of modified stem cells, showed an increase in the number of CD4 T-helper immune cells– targets of HIV infection - with a simultaneous decrease in the level of HIV activity in the blood.

However, the researchers note a potential weak point of the experiment. The fact is that human immune cells do not provide a full restoration of the immune system in the body of humanized mice. Therefore, it is possible that HIV mutates more slowly in this model than in the human body. However, they believe that this problem can be solved by using several modified receptors, and have already begun work on the creation of T-cell receptors specific to different components of HIV.

Article by Scott G. Kitchen et al. In Vivo Suppression of HIV by Antigen Specific T Cells Derived from Engineered Hematopoietic Stem Cells is published in the journal PLoS Pathogens.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of California, Los Angeles:
UCLA-engineered stem cells seek out and kill HIV in living organisms.

13.04.2012

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