Several years ago, Edelman began using endothelial cells, grown within a scaffold made of denatured, compressed collagen (a protein that makes up much of human connective tissue), as an implantable device. The "matrix-embedded endothelial cells" served as a convenient unit that could be produced in bulk, tested for quality control, retained intact for months and implanted immediately when needed. This way, the healthiest cells could be selected to secrete all of the chemicals normally released by endothelial cells and placed in multiple locations in the body to control disease.

In clinical trials these implants were placed around blood vessels after vascular surgery and controlled local clotting and infection better than devices without cells. Significantly, because the endothelial cells were associated with a matrix mimicking their natural state, even cells from other people could be implanted without being rejected by the patients' immune systems. No major side effects were seen in the clinical trials,

"Blood vessels and endothelial cells are the perfect regulatory units and our synthetic device recapitulated these control units perfectly," says Franses. Blood vessels penetrate to the deepest recesses of tumors, and in doing so carry the powerful regulatory endothelial cells as close to cancer cells as possible. The extracellular matrix backbone of the vessels can keep the endothelial cells healthy and the healthy endothelial cells control nearby cancer cells. "This is what we mimicked with our devices," he says. "In a sense it is like putting a cellular policeman on the corner of every tumor neighborhood."

In one mouse experiment reported in the new paper, endothelial cell implants significantly slowed tumor growth and prevented gross destructive change in tumor structure. Another experiment showed that cancer cells that had been grown in the secretions of endothelial cells were less able than standard cancer cells to metastasize and colonize the lungs of mice.

The new findings could also explain why drugs that suppress angiogenesis - growth of new blood vessels - have shown only transient and moderate benefit for cancer patients thus far. "You starve the tumor of its blood supply, but you also damage tumor blood vessel endothelial cells, so when the tumor comes back, there's nothing to keep it in check. The vessels feed the tumor but their endothelial cells control the cancer cells within. Giving the endothelial cells without the blood vessels provides the best of both worlds and perhaps one day could provide new means of cancer therapy," says Edelman.

Source: Massachusetts Institute of Technology