Featured Research

from universities, journals, and other organizations

Engineered stem cells seek out and kill HIV in living mice

Date:
April 12, 2012
Source:
University of California, Los Angeles (UCLA), Health Sciences
Summary:
Expanding on previous research providing proof-of-principle that human stem cells can be genetically engineered into HIV-fighting cells, a team of researchers have now demonstrated that these cells can actually attack HIV-infected cells in a living organism.

Human immunodeficiency virus (HIV).
Credit: Photo credit: C. Goldsmith/public domain

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 have now demonstrated that these cells can actually attack HIV-infected cells in a living organism.

Related Articles


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.


Story Source:

The above story is based on materials provided by University of California, Los Angeles (UCLA), Health Sciences. The original article was written by Enrique Rivero. Note: Materials may be edited for content and length.


Journal Reference:

  1. Scott G. Kitchen, Bernard R. Levin, Gregory Bristol, Valerie Rezek, Sohn Kim, Christian Aguilera-Sandoval, Arumugam Balamurugan, Otto O. Yang, Jerome A. Zack. In Vivo Suppression of HIV by Antigen Specific T Cells Derived from Engineered Hematopoietic Stem Cells. PLoS Pathogens, 2012; 8 (4): e1002649 DOI: 10.1371/journal.ppat.1002649

Cite This Page:

University of California, Los Angeles (UCLA), Health Sciences. "Engineered stem cells seek out and kill HIV in living mice." ScienceDaily. ScienceDaily, 12 April 2012. <www.sciencedaily.com/releases/2012/04/120412182253.htm>.
University of California, Los Angeles (UCLA), Health Sciences. (2012, April 12). Engineered stem cells seek out and kill HIV in living mice. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/2012/04/120412182253.htm
University of California, Los Angeles (UCLA), Health Sciences. "Engineered stem cells seek out and kill HIV in living mice." ScienceDaily. www.sciencedaily.com/releases/2012/04/120412182253.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com
Ebola: Life Without School in Guinea

Ebola: Life Without School in Guinea

AFP (Nov. 21, 2014) Following the closure of schools and universities in Guinea because of the Ebola virus, students look for temporary work or gather in makeshift classrooms to catch up on their syllabus. Duration: 02:14 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins