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April 9, 2019
Bioengineered vessels transform into living blood vessels
At a Glance
- Bioengineered vessels that were implanted in people to aid with kidney dialysis matured into living blood vessels.
- The 4-year study demonstrates that the vessels, called human acellular vessels, can be integrated into human tissues.
The kidneys filter waste and water from blood. People with kidney failure can use a dialysis machine to filter blood. It removes blood from a vein in the arm, filters it outside the body, and returns clean blood to another part of the vein.
If dialysis is needed often, the vein becomes more likely to collapse. To help prevent this, a surgeon can connect an artery in the arm to a vein. The extra blood from the artery makes the vein wider and thicker. That makes it easier to insert the needle in the vein for dialysis.
Another option is for the surgeon to graft a loop of natural blood vessel or an artificial vessel to the vein. Patients receiving such grafts are at risk of inflammation and infections. Other drawbacks are that availability of natural blood vessels is limited, and artificial grafts don’t integrate into the body’s tissues.
To develop an improved approach, a team of researchers led by Dr. Heather Prichard of Humacyte Inc. created biologically engineered vessels called human acellular vessels. Previous studies suggested that patients’ cells could grow on the bioengineered vessels in a process called recellularization. In their new study, they assessed the long-term growth and maturation of these bioengineered vessels when implanted in people. The work was supported in part by NIH’s National Heart, Lung, and Blood Institute (NHLBI). Their findings appeared on March 27, 2019, in Science Translational Medicine.
The research team seeded tubes made of a biodegradable mesh scaffold with cells from cadaver blood vessels. Fluid and nutrients were pumped through the tubes in devices called bioreactors. Over 2 months, the cells grew in the mesh and produced their own natural matrix as the original scaffold began to dissolve. The team then processed the tubes to remove the cells but retain the cell products, like collagen and other matrix proteins, that now formed the tube-like structures. The resulting tubes had a shape and strength similar to natural blood vessels.
The bioengineered vessels were grafted between an artery and vein above the elbow in 60 adults with end-stage kidney failure. Ultrasound imaging showed that blood was flowing through the grafted vessels. Participants were given dialysis through needles in the vessels three times a week.
The frequent needle pricks caused some of the vessels to be blocked by blood clots or to bulge. Sixteen injured segments were removed from 13 people at various times between 4 weeks and 4 years. Microscope analysis revealed that over time cells from the participants had formed layers of tissue resembling natural blood vessels.
The team also noticed that networks of tiny vessels called capillaries had formed to foster blood circulation. In addition, the bioengineered vessels had integrated into nearby tissues. The team did not see signs of inflammation in the vessels.
“As a regenerative medicine product, we’re excited to see evidence of functional tissue recellularization in actual patients, which may have the potential to enhance long term efficacy and safety,” Prichard says.
In addition to helping people with kidney failure who need frequent dialysis, such bioengineered blood vessels could also be used by surgeons to repair vessels in the chest and abdomen.
—by Geri Piazza
- Next-Generation Replacement Blood Vessels Target Kidney and Heart Disease
- Bioengineered Blood Vessel Grafts Grow in Animals
- Stem Cells Coaxed To Create Working Blood Vessels
- Why Many Vein Grafts Fail
- Tissue Engineering and Regenerative Medicine
References: Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation. Kirkton RD, Santiago-Maysonet M, Lawson JH, Tente WE, Dahl SLM, Niklason LE, Prichard HL. Sci Transl Med. 2019 Mar 27;11(485). pii: eaau6934. doi: 10.1126/scitranslmed.aau6934. PMID: 30918113.
Funding: NIH’s National Heart, Lung, and Blood Institute (NHLBI) and Humacyte, Inc.