Stem cells engineered to become targeted drug factories

A group of Brigham and Women’s Hospital, and Harvard Stem Cell Institute researchers, and collaborators at MIT and Massachusetts General Hospital have found a way to use stem cells as drug delivery vehicles. The researchers inserted modified strands of messenger…

A group of Brigham and Women’s Hospital, and Harvard Stem Cell Institute researchers, and collaborators at MIT and Massachusetts General Hospital have found a way to use stem cells as drug delivery vehicles.

The researchers inserted modified strands of messenger RNA into connective tissue stem cells — called mesenchymal stem cells — which stimulated the cells to produce adhesive surface proteins and secrete interleukin-10, an anti-inflammatory molecule. When injected into the bloodstream of a mouse, these modified human stem cells were able to target and stick to sites of inflammation and release biological agents that successfully reduced the swelling.

“If you think of a cell as a drug factory, what we’re doing is targeting cell-based, drug factories to damaged or diseased tissues, where the cells can produce drugs at high enough levels to have a therapeutic effect,” said research leader Jeffrey Karp, PhD, a Harvard Stem Cell Institute principal faculty member and Associate Professor at the Brigham and Women’s Hospital, Harvard Medical School, and Affiliate faculty at MIT.
Karp’s proof of concept study, published in the journal Blood, is drawing early interest from biopharmaceutical companies for its potential to target biological drugs to disease sites. While ranked as the top sellers in the drug industry, biological drugs are still challenging to use, and Karp’s approach may improve their clinical application as well as improve the historically mixed, clinical trial results of mesenchymal stem cell-based treatments.
Mesenchymal stem cells have become cell therapy researchers’ tool of choice because they can evade the immune system, and thus are safe to use even if they are derived from another person. To modify the cells with messenger RNA, the researchers used the RNA delivery and cell programming technique that was previously developed in the MIT laboratory of Mehmet Fatih Yanik, PhD. This RNA technique to program cells is harmless, as it does not modify the cells’ genome, which can be a problem when DNA is used (via viruses) to manipulate gene expression.
“This opens the door to thinking of messenger RNA transfection of cell populations as next generation therapeutics in the clinic, as they get around some of the delivery challenges that have been encountered with biological agents,” said Oren Levy, PhD, co-lead author of the study and Instructor of Medicine in Karp’s lab. The study was also co-led by Weian Zhao, PhD, at University of California, Irvine who was previously a postdoctoral fellow in Karp’s lab.
One such challenge with using mesenchymal stem cells is they have a “hit-and-run” effect, since they are rapidly cleared after entering the bloodstream, typically within a few hours or days. The Harvard/MIT team demonstrated that rapid targeting of the cells to the inflamed tissue produced a therapeutic effect despite the cells being rapidly cleared. The scientists want to extend cell lifespan even further and are experimenting with how to use messenger RNA to make the stem cells produce pro-survival factors.
“We’re interested to explore the platform nature of this approach and see what potential limitations it may have or how far we can actually push it,” Zhao said. “Potentially, we can simultaneously deliver proteins that have synergistic therapeutic impacts.”

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is based on materials provided by Harvard University.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:
O. Levy, W. Zhao, L. J. Mortensen, S. LeBlanc, K. Tsang, M. Fu, J. A. Phillips, V. Sagar, P. Anandakumaran, J. Ngai, C. H. Cui, P. Eimon, M. Angel, C. P. Lin, M. F. Yanik, J. M. Karp. mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation. Blood, 2013; 122 (14): e23 DOI: 10.1182/blood-2013-04-495119

Note: If no author is given, the source is cited instead.

Search ScienceDaily
Number of stories in archives: 144,186

 

Interested in ad-free access? If you’d like to read ScienceDaily without ads, let us know!

more breaking science news

Social Networks
Follow ScienceDaily on Facebook, Twitter, and Google:

Recommend ScienceDaily on Facebook, Twitter, and Google +1:

Other social bookmarking and sharing tools:

Breaking News
… from NewsDaily.com

more science news
In Other News …
more top news
Science Video News

Unraveling Brain Tumors
Brain tumor researchers have found that brain tumors arise from cancer stem cells living within tiny protective areas formed by blood vessels in the. …  > full story

Strange Science News
Free Subscriptions
… from ScienceDaily

Get the latest science news with our free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:
Email Newsletters
RSS Newsfeeds
Feedback
… we want to hear from you!

Tell us what you think of ScienceDaily — we welcome both positive and negative comments. Have any problems using the site? Questions?
Leave Feedback