Discovery reveals possible way to engineer blood vessels to deliver drugs

Children's Hospital Boston researchers believe they have may have found a way to genetically engineer blood vessels to secrete recombinant, protein-based drugs directly into the bloodstream--on demand. Their first success involved using the concept to reverse anemia in mice.

Future testing, they said, could expand the idea of developing special blood vessels that secrete and deliver protein-based drugs--made previously in bioreactors by engineered cells--to treat patients with hemophilia, hepatitis C and multiple sclerosis. The discovery could also allow for fewer injections of expensive recombinant drugs, doses of which are needed frequently. The proof-of-concept study is highlighted in the Nov. 17 issue of Blood.

"The paradigm shift here is 'why don't we instruct your own cells to be the factory?'" lead investigator Juan Melero-Martin said in a statement. Melero-Martin teaches at Harvard Medical School and is a member of the hospital's Department of Cardiac Surgery

Researchers worked on anemic mice, and were able to reverse their condition by deploying engineered vessels that secreted erythropoietin.

To concoct their special vessels, they first isolated endothelial colony-forming cells from human blood. Next, they inserted a gene that told the cells to produce erythropoietin. Mesenchymal stem cells were the next ingredient, and then those enhanced cells were suspended in a gel. Scientists injected the mixture under the skin of the anemic mice, after which the cells began to form groups of blood vessels lined with the engineered cells. The cells linked onto the mice's blood vessels within a week and began to release the erythropoietin treatment into the bloodstream.

Another protein linked to the erythropoietin encoding gene kept the drug secretion off until the mice drank doxycycline in their water, which turned on production. Without the oral drug, the erythropoietin production turned off.

- here's the release

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