Researchers from the UCLA AIDS Institute and the Institute for Stem Cell Biology and Medicine have demonstrated for the first time that human embryonic stem cells can be genetically manipulated and coaxed to develop into mature T-cells, raising hopes for a gene therapy to combat AIDS.
The study, to be published the week of July 3 in the online edition of the Proceedings of the National Academy of Sciences, found that it is possible to convert human embryonic stem cells into blood-forming stem cells that in turn can differentiate into the helper T-cells that HIV specifically targets. T-cells are one of the body's main defenses against disease.
The results mark the first time that scientists have been able to derive T-cells out of human embryonic stem cells, said Zoran Galic, assistant research biologist, and lead researcher on the study.
"This tells you that you may be able to use human embryonic stem cells to treat T cell and other blood diseases. This could be a very important weapon in the fight against AIDS," Galic said.
The study is available at http://www.pnas.org/papbyrecent.shtml.
In their study, the researchers cultured human embryonic stem cells, which were incubated on mouse bone marrow support cells, which in turn converted them into blood forming cells. Those cells were then injected into a human thymus gland that had been implanted in a mouse, and the thymus then changed those blood-forming cells into T-cells. Located just above the heart in humans, the thymus is the organ where T-cells develop. It gradually shrinks in adults, weakening the immune system over time.
These results indicate that it is possible to decipher the signals that control the development of embryonic stem cells into mature T-cells, said study co-author Jerome Zack, associate director of the UCLA AIDS Institute, and professor of medicine and of microbiology,
immunology and molecular genetics at the David Geffen School of Medicine at UCLA.
"That way we can eventually repopulate the immune system in patients needing T-cells," Zack said.
This in turn could give rise to gene therapy approaches to treat other diseases involving T-cells. In addition to HIV, for instance, the technique could be used to treat severe combined immunodeficiency, or the "bubble boy disease," which leaves its victims without a working immune system, forcing them to a life in an antiseptic, germ-free environment.
Other researchers who participated in this study are Scott G. Kitchen, Amelia Kacena, Aparna Subramanian, Bryan Burke and Ruth Cortado, all with the David Geffen School of Medicine at UCLA.
The National Institutes of Health funded the study.
Established in 1992, the UCLA AIDS Institute 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 science, 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.
The Institute for Stem Cell Biology and Medicine was launched on March 6, 2005, with a UCLA commitment of $20 million over five years. The institute brings together geneticists, engineers, ethicists, chemists, policy experts, pathologists, immunologists, oncologists, hematologists and scientists from other disciplines to uncover the mysteries of the growth and development of adult and embryonic stem cells. The institute is a collaboration of the David Geffen School of Medicine at UCLA, UCLA's Jonsson Cancer Center, the UCLA Henry Samueli School of Engineering and Applied Science, and the UCLA College of Letters and Science.
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