MANILA, Philippines – Because they are rich in stem cells, the cord blood of babies is being stored in blood banks, fueling a growing industry. Human stem cells, after all, have been credited with vast medical powers.
But can stem cells be used to cure one of the major scourges of the modern age: HIV-AIDS?
A series of studies conducted by researchers at the University of California in Los Angeles (UCLA) suggest that this might indeed be possible. In the most recent study, published on April 12 in the journal PLoS Pathogens, the researchers demonstrated that these stem cells can actually attack HIV-infected cells in a living organism.
Genetically manipulated stem cells
The new study expands on previous research that establishes human stem cells can be genetically engineered into HIV-fighting cells. This is essential in the early stages of development of a drug.
This is the first time that stem cells, which are being engineered to form immune cells that target HIV, have been shown to be effective in suppressing the virus in an animal’s living tissues. This is according to 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. Kitchen is also 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. They then identified the molecule known as the T cell receptor, which guides the T cell and aids it in recognizing and killing HIV-infected cells.
While able to destroy HIV-infected cells, these T cells do not exist in great enough quantities to flush the virus from the body. The researchers thus cloned the receptor and used this to genetically engineer human blood stem cells. They then placed the engineered stem cells into the 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 with an individual in much the same way that an organ is matched with a transplant patient.
Tests on “humanized” mice
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.
This was done 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, 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. The tests involving the CD4 cells were conducted 2 weeks and 6 weeks after introducing the engineered cells.
The test results indicated that the engineered cells were capable of developing and migrating to the organs to fight infection there.
Weakness of the study
The researchers did note a potential weakness in the study: Because human immune cells reconstituted better at a lower level in the humanized mice than in humans, the mice’s immune systems were mostly, though not completely, reconstructed.
This means HIV may be slower to mutate in 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. – Rappler.com