UCLA-Engineered Stem Cells Seek Out and Kill HIV in Living Organisms
By Enrique Rivero
April 12, 2012
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.
Comment by: michael
Sat., May. 19, 2012 at 4:24 am EDT
this is an extraordinary approach. there is already research in regards to taking a biopsy sample from a person, breaking it down and to form blank adult stem cells and train it to act like embryo stem cells to grow into any organ tissue you want.
combine that research to this, and you can use it to implant it onto reservoir hiv hideouts and flush out the remaining hiv that HAART cannot get into.
this also can help boost the immune system to normal levels and reconstitute it to give it a second wind to do battle against any remaining virus in the body. a reconstituted immune system along with newly implanted stem cell tissue in the reservoir areas that targets the virus is as close to a cure as you can have.
this is why stem cell research works. it replaces damaged areas of your body, including the brain.
make noise and let the next phase in the HIV fight be about expediting stem cell research, not just for HIV, but in all areas of medicine.
Comment by: Jay
Thu., May. 17, 2012 at 4:06 pm EDT
My question is that this is a different approach to fight HIV then the Sangamo trial approach were the reseachers are trying to functionally cure HIV by modifying the CCR5 receptor to be HIV resistant, ok these reseachers are making CD8 cells that actually attack HIV and destroy those infected cells so why don't they just combine both of these avenues to combat the virus and destroy it that way, it seems like the researchers are not working together to destroy this epidemic which they should be doing, I understand they all want the glory of being the one that comes up the strategy of defeating HIV but they will all get credit for it in the end I just think they need to share ideas with each other because HIV is a universal problem.
Comment by: Billy
Wed., May. 16, 2012 at 10:15 am EDT
Since I have been infected, no matter how I try to fool myself into feeling good---the pains that come with the disease are not pleasant or either the side-effects of the Rx's. Let us be a "reaL" progressive country and put this good work to the test now. I know about the mutation of the virus which is happening on persons 10 years plus on the cocktail and just lost my partner of 23+ year to an HIV related cancer. If you want a person to try this out on, I am willing. I feel the dragging the feet syndrome has been going on too long. Let's get started!
Comment by: michael
Sun., May. 13, 2012 at 4:29 am EDT
really? almost a month old story and this is not getting any attention?
this is exactly why stem cell research is vital. it's geared more towards cure rather than treatment.
pair this with the research of being able to take a tissue sample from a person, break the tissue apart to gather building blocks to form stem cell out of to grow and teach it to form something else is breakthrough work.
reconstituting the immune system more naturally without the dozen side effects of drugs and perhaps more cost effective if the results are permanent. no more taking toxic drugs for the rest of your life.
Comment by: Harold S.
Fri., May. 11, 2012 at 8:06 am EDT
Let me be the first to try the stem cell therapy!! Too not take drugs or as such a lethal amount of them have your body wracked with all the other compilations YES,YES,YES!!!! Think of all the other blood pathogens viruses this could help !!!
Comment by: Cathy I.
Fri., May. 11, 2012 at 7:25 am EDT
So basically, manufacturing stem cells to be used in clinical trials is still years away. Does that mean more than five years? More than ten?
How long are clinical trials done before a specific approach gets approval, and what success rate would be required before a method is used as regular treatment?
Assuming eradication of the virus is successful, would the next step in research be determining whether those treated could be reinfected?
Comment by: Christina
(Des Moines Iowa)
Fri., May. 11, 2012 at 5:34 am EDT
This is awesome news! I am Hiv/Aids infected since my diagnosis in 1988. It has been a long and horible virus to fight. My question is how long before this could become a treatment for those of us who are in the late stages of the disease? Could we be the ones to get this treatment first? This is wonderful and hopeful news! Thank You Christina
Comment by: Mark G.
(South Africa )
Fri., May. 11, 2012 at 5:25 am EDT
I am so pleased to see progress in research.I was begining to think the drug companies were not looking for a cure so that they make money of the backs of the HIV Pos people for ever.
Comment by: Elizabeth
Fri., May. 11, 2012 at 3:53 am EDT
While watching the video my heart sank towards the end at the words "We still are years away from testing this in patients".
Please, if people with lots of money are reading this page, please donate generously to the UCLA AIDS Institute. WE ARE DESPERATE FOR A CURE. And many of us can't wait for years. HIV will have either killed us by then or caused us serious problems despite the medications we're taking to fight it.
Comment by: Annie U.
Fri., May. 11, 2012 at 12:07 am EDT
Are there test of natural herbs to see if it can kill this virus in muse and human? If not can that aspect be looked at so that it could be widely available to masses that are infected with this killer virus all over the world.
Comment by: Scott
Fri., May. 18, 2012 at 5:49 am EDT In the 90's drug companies said they would research using herbs with pharma to find a cure for HIV but as soon as they developed the drugs and played on fears of no vaccine developement any time soon-they suddenly claimed the only sure thing was the drugs and stopped research of herbal solutions for treatment.Now they claim herbs interact with HIV meds and shouldn't be used while on meds.As patients we should demand money go to research natural treatments for HIV.
Comment by: Synjewel
Thu., May. 10, 2012 at 11:26 pm EDT
I would be interest in doing study on myself in the name
Of science in hope hope
Of eradicating HIV from my body
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