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Investigators Create Therapy-Producing Blood Vessels in Mice

Researchers from the Children’s Hospital in Boston, Harvard Medical School and University of North Carolina at Chapel Hill genetically engineered blood vessels to secrete a recombinant, protein-based drug into the bloodstream of anemic mice, reversing the condition. The lead author of the study was Juan Melero-Martin, PhD, Assistant Professor, Department of Surgery, Harvard Medical School. He is on staff in the Department of Cardiac Surgery, Children’s Hospital Boston.


Melero-Martin and his colleagues extracted endothelial cells, which line the interior surface of blood vessels, from human blood, and then inserted a gene that directed the production of the hormone erythropoietin (EPO). A protein produced by the kidney, EPO promotes the formation of red blood cells in the bone marrow, which carry oxygen to vital organs. Disease-compromised kidneys do not manufacture adequate amounts of EPO, resulting in anemia.


Investigators then combined the endothelial cells with mesenchymal cells (multipotent stem cells that can differentiate into a variety of cell types), encapsulated them in a gel and injected the therapy under the skin of the anemic mice. Within a week, the engineered cells activated the formation of new blood vessels that manufactured EPO, releasing it into the bloodstream and correcting the animals’ anemia. This method could relieve human patients of the need for frequent EPO injections, which can be costly.


The findings prompted investigators to imagine the potential for using such a technique to target blood vessels to produce other therapeutic proteins for the treatment of conditions such as hepatitis C, multiple sclerosis and hemophilia. “The paradigm shift here is ‘why don't we instruct your own cells to be the factory?’” said Melero-Martin.


The study, “Induction of Erythropoiesis Using Human Vascular Networks Genetically Engineered for Controlled Erythropoietin Release,” was published in the November 17, 2011, issue of the journal Blood.




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