Research with sheep demonstrates utility of new synthetic blood vessels

Children born with heart defects often undergo multiple surgeries throughout their lives because the synthetic materials used to replace blood vessels and heart valves do not grow with the patient (1). The implant needed for an infant will be far too small once that child grows up.  In addition, if the replacement is grafted from another person or from an animal, the child may need to take immunosuppressant drugs for the rest of their lives to prevent their body from rejecting the graft.

Scientists from the University of Minnesota, led by Dr. Robert Tranquillo, tested a new technique in lambs allowing for an implanted graft to grow with the patient (2). The scientists coaxed cells, called fibroblasts, into growing a tube of collagen—a stretchy matrix of protein that gives structure to skin and blood vessels. Once the tube was made, the researchers used a special solution to remove the fibroblast cells. What remained—a flexible collagen vessel—was implanted it into the pulmonary artery of an 8-week-old lamb. Since collagen is the natural structural component of blood vessels, the scientists expected that the lamb’s body would accept the graft and that the new vessel would grow with the animal. And that’s exactly what the researchers saw. Forty-two weeks after implantation, scientists discovered that the replacement artery enlarged in diameter and volume as the lamb grew. The implanted artery had also been fully colonized by the lamb’s own cells and had all the mechanical and biological features of a native artery.

"Researchers are working to create an “off-the-shelf” material that doctors can implant in a patient, and it can grow in the body. This research has the potential to prevent the need for repeated surgeries in some children with congenital heart defects." - Image courtesy of University of Minnesota
“Researchers are working to create an “off-the-shelf” material that doctors can implant in a patient, and it can grow in the body. This research has the potential to prevent the need for repeated surgeries in some children with congenital heart defects.” – Image courtesy of University of Minnesota

This finding builds off of Dr. Tranquillo’s extensive research into cardiovascular tissue engineering (1, 3, 4, 5). Previously, his laboratory has developed “tissue-equivalents” to replace diseased or damaged arteries.  He and his team are also working to develop new heart valves that can be introduced into the patient via a catheter instead of open heart surgery.

Earlier attempts to create implants that grew with the patient required extracting cells from the patient, waiting for them to grow in culture, seeding them within a bio-degradable scaffold, and then implanting the structure back into the patient. These attempts were successful, but since each artery was custom-made, this technique was costly, and would require developing reliable ways to extract and culture cells from patients before it could be widely used. In this new method, the artery does not need to be grown from the patient’s cells—any fibroblasts will work—so replacement arteries can be mass-produced and used ‘off-the-shelf’. In addition, all cells are washed from the collagen tube before implantation, so there’s no risk of rejection by the patient’s immune system. Most importantly, if these experiments from lambs carry over to humans, these grafts should be fully accepted by the patient and grow along with them, meaning that an infant who receives one of these grafts will have a permanent, fully functional blood vessel that won’t need replacement as she or he grows. Tranquillo and his team are working to develop replacement vessels that include valves (3).

"Robert Tranquillo, department head and professor of biomedical engineering, is leading tissue engineering research. He and his team are growing tissue that could one day replace a defective pediatric heart valve." - Image Courtesy of the University of Minnesota
“Robert Tranquillo, department head and professor of biomedical engineering, is leading tissue engineering research. He and his team are growing tissue that could one day replace a defective pediatric heart valve.” – Image courtesy of the University of Minnesota

Many anatomical and physiological similarities exist between the cardiovascular systems of sheep and humans, and large animal models, such as the sheep, are integral in moving research from the laboratory into the clinic. Dr. Tranquillo’s work with sheep and lambs is advancing our understanding of tissue bio-mechanics and could one day allow natural heart valve and blood vessel replacement.

Samuel Henager
Science Policy Fellow, FASEB
Graduate Student, Johns Hopkins University

References:

(1) Implantation of a tissue-engineered tubular heart valve in growing lambs
Reimer, J.M., Syedain, Z.H., Haynei, B., Lahti, M., Berry, J. and R.T. Tranquillo
Ann Biomed Eng (2016). doi:10.1007/s10439-016-1605-7

(2) Tissue engineering of a cellular vascular grafts capable of somatic growth in young lambs
Syedain, Z.H., Reimer, J. M., Lahti, M., Berry, J., Johnson, S., and R.T. Tranquillo
Nat Comm (2016). doi:10.1038/ncomms12951

(3) 6-month aortic valve implantation of an off-the-shelf tissue-engineered valve in sheep
Syedain, Z.H., Reimer, J.M., Schmidt, J.B., Lahti, M., Berry, J., Bianco, R. and R.T. Tranquillo
Biomaterials 73:175-84 (2015).

(4) Implantation of completely biological engineered grafts following decellularization into the sheep femoral artery
Syedain, Z.H., Meier, L.A., Lahti, M.T., Johnson, S.L., Hebbel, R.P and R. T. Tranquillo
Tissue Eng Part A 20: 1726-34 (2014).

(5) Aligned human microvessels formed in 3D fibrin gel by constraint of gel contraction
Morin, K.T., Smith, A.O., Davis, G.E., and R.T. Tranquillo
Microvasc Res 90:12-22 (2013).