Ready-made blood vessels that surgeons could take off the shelf and implant into patients may not be as far-fetched as they sound. Researchers report today in Science Translational Medicine a novel way of using human cells to generate blood vessels that may function in people without prompting an immune reaction. Unlike other engineered vessels, these can be stored for up to 12 months, which could allow hospitals to keep them on hand for immediate use in patients who need them.
Doctors perform blood-vessel transplants in heart bypass surgery and in dialysis patients. They often take the veins from one of the patients' own legs or elsewhere in the body. But sometimes physicians can't find suitable vessels, and transplants from tissue donors or even from animals have not proven safe or effective. To meet the need in such cases, some researchers are growing sheets of a patient's own cells in the lab and wrapping them to make a vessel. But this process is expensive and can take 9 months or longer—which is often too long for patients to wait.
Shannon Dahl, a tissue engineer at Humacyte, a biotechnology company in Morrisville, North Carolina, and her colleagues have now combined several techniques to explore another way to produce replacement blood vessels. The strategy is to seed human smooth muscle cells, taken from donated cadavers, onto a tubular scaffold made from a biodegradable polymer called polyglycolic acid. As the cells grow to cover the scaffold, they produce collagen and other extracellular matrix (ECM) proteins that replace the degrading scaffold. The researchers then use detergent to remove the cells, leaving a cell-free blood vessel that the researchers theorized could be stored for months and would not prompt an immune reaction in the recipient.
The researchers compared vessels made with seed cells from one donated cadaver with those made from the pooled cells from several donors. The pooled cells produced vessels just as strong as those from single donors. That's good news, Dahl says, because pooling these seed cells would make it possible to grow more vessels in a single batch, lowering the vessels' cost.
The researchers then transplanted the engineered blood vessels into the arms of eight baboons. They remained functional and free of clots for up to 6 months and didn't seem to prompt an immune response despite being composed of human collagen and ECM. Dahl and her colleagues also made smaller vessels—suitable for coronary bypass—from dog cells and transplanted those into five dogs, where they stayed clear of blockages for up to a year. In both models, the new vessels were soon populated by several of the types of cells present in normal blood vessels, suggesting that the animals' bodies were tolerating the transplants.
Although the number of experimental animals in Dahl's study was small, says Robert Nerem, a bioengineer at the Georgia Institute of Technology in Atlanta, the results are encouraging. The fact that the engineered vessels can be easily stored suggests that surgeons could keep a ready supply on hand. "If you've got to do bypass surgery, frequently it is not an elective procedure where you sit around waiting for weeks. You really want this to work off the shelf," he says.
Dahl says she and her colleagues are now "laying the groundwork" for how they might safely begin to test the vessels in human patients. Although the animal results are preliminary, she says, they are encouraging enough that "it is worth our energy to evaluate the technology in the clinic."