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Engineered, drug-secreting blood vessels reverse anemia in mice
Date:11/15/2011

Patients who rely on recombinant, protein-based drugs must often endure frequent injections, often several times a week, or intravenous therapy. Researchers at Children's Hospital Boston demonstrate the possibility that blood vessels, made from genetically engineered cells, could secrete the drug on demand directly into the bloodstream. In the November 17 issue of the journal Blood, they provide proof-of-concept, reversing anemia in mice with engineered vessels secreting erythropoietin (EPO).

The technology could potentially be used to deliver other proteins such as Factor VIII and Factor IX for patients with hemophilia, alpha interferon for hepatitis C and interferon beta for multiple sclerosis, says the study's principal investigator, Juan Melero-Martin, PhD, of the Department of Cardiac Surgery at Children's.

Such drugs are currently made in bioreactors by engineered cells, and are very expensive to make in large amounts. "The paradigm shift here is, 'why don't we instruct your own cells to be the factory?'" says Melero-Martin, also an assistant professor at Harvard Medical School.

The researchers created the drug-secreting vessels by isolating endothelial colony-forming cells from human blood and inserting a gene instructing the cells to produce EPO. They then added mesenchymal stem cells, suspended the cells in a gel, and injected this mixture into the mice, just under the skin. The cells spontaneously formed networks of blood vessels, lined with the engineered endothelial cells. Within a week, the vessels hooked up with the animals' own vessels, releasing EPO into the bloodstream.

Tests showed that the drug circulated throughout the body and reversed anemia in the mice, both induced by radiation (as often occurs in cancer patients) and by loss of kidney tissue (modeling chronic kidney failure). Mice with the vessel implants had significantly higher hematocrits (a measure of red blood cell concentration) and rec
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Contact: Children's Hospital Boston
Colleen.Connolly@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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