The pharmaceutical factory itself
Mobile "pharmaceutical plants" from engineered stem cells
LifeSciencesToday based on materials from Harvard Stem Cell Institute: Stem Cells Engineered to Become Targeted Drug FactoriesScientists from Brigham and Women's Hospital and Harvard Stem Cell Institute, together with their colleagues from the Massachusetts Institute of Technology and Massachusetts General Hospital, have found a way to use stem cells as a means of targeted delivery of biological drugs.
The researchers introduced modified matrix RNA chains into connective tissue stem cells – mesenchymal stem cells – stimulating the synthesis of adhesive surface proteins and the secretion of the powerful anti-inflammatory cytokine interleukin-10. When the modified human stem cells entered the bloodstream of the mouse, they targeted the area of inflammation and rushed to it, releasing biological agents that successfully reduced edema.
Engineered mesenchymal stem cells "induced" on the inflammation zone,
the immunosuppressive cytokine interleukin-10 is secreted. (Photo: Jeffrey Karp)"If we look at the cell as a drug factory, then what we are doing is orienting these cell factories to damaged or diseased tissues, where they can produce medicinal substances at a level high enough to have a therapeutic effect," comments the study's leader Jeffrey Karp, PhD, senior Lecturer at the Harvard Stem Cell Institute, Associate Professor at Brigham Women's Hospital, Harvard Medical School, visiting lecturer at the Massachusetts Institute of Technology.
A study published in the journal Blood by Dr. Karp and his colleagues (Levy et al., mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation), which is proof of the possibility of using such mobile "pharmaceutical plants", has already attracted the attention of biopharmaceutical companies. They were interested in the possibility of targeted delivery of biological drugs directly to the focus of inflammation. Entering the top-selling pharmaceutical industry, biological drugs are still difficult to use, and the approach developed by Dr. Karp can raise their clinical significance to a new level, as well as clarify the evaluation of the results of clinical trials based on mesenchymal stem cells methods, which are still regarded as ambiguous.
Mesenchymal stem cells have become the tool of choice for scientists involved in the development of cell therapy methods, their ability to evade the attacks of the immune system has made them: they are safe even if they are received from another person. To modify them with the help of matrix RNA, the researchers used a technique of RNA delivery and cellular programming, previously developed at the Massachusetts Institute of Technology by the laboratory of Mehmet Fatih Yanik (Mehmet Fatih Yanik), PhD. This RNA-based programming technique is harmless because it does not change the genome of cells, which is a problem if DNA delivered to the cell by viruses is used to manipulate gene expression.
"This opens the way to the use of transfection of cell populations with matrix RNAs as the next generation of clinical therapy, as this technique allows to bypass some of the delivery problems that scientists have encountered when working with biological agents," says co–lead author of the study Oren Levy, PhD.
One of the main problems in the use of mesenchymal stem cells is the insufficient duration of the effect they produce, since after entering the blood they are quickly – usually within a few hours or days – excreted from the body. Dr. Karp and his colleagues have demonstrated that specific "targeting" of inflamed tissue allows cells to have a therapeutic effect, despite rapid elimination. To increase the life expectancy of stem cells, scientists have begun experiments on the use of matrix RNAs encoding factors that contribute to their survival.
"We want to explore this approach as a platform and find out what its potential limitations and opportunities are," says Weian Zhao, PhD, co–director of the work. "Theoretically, simultaneous delivery of proteins with synergistic therapeutic effects is possible."
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