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 strands² of messenger RNA into connective tissue stem cells -- called mesenchymal（间叶细胞的） stem cells -- which stimulated³ the cells to produce adhesive⁴ surface proteins and secrete⁵ interleukin-10, an anti-inflammatory molecule⁶. 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 swelling⁷.

 

"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 therapeutic⁸ effect," said research leader Jeffrey Karp, PhD, a Harvard Stem Cell Institute principal faculty⁹ member and Associate Professor at the Brigham and Women's Hospital, Harvard Medical School, and Affiliate¹⁰ 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 evade¹¹ the immune system, and thus are safe to use even if they are derived¹² from another person. To modify the cells with messenger RNA, the researchers used the RNA delivery and cell programming technique that was previously¹³ 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 DNA¹⁴ is used (via viruses) to manipulate gene¹ 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 Levy¹⁵, PhD, co-lead author of the study and Instructor¹⁶ 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.

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