Study Sheds Light On Formation of Tissue-Engineered Vascular Grafts to Repair Heart Defect

Feb 22, 2010

(PhysOrg.com) -- A Yale School of Medicine study provides new understanding of the mechanisms that underlie how tissue engineered vascular grafts (TEVG) work. The paper is published this week in the online Early Edition of the Proceedings of the National Academy of Sciences.

TEVG are specially-designed vascular grafts that can be used in congenital heart surgery because they possess growth potential. They are made by seeding an individual’s own cells onto a biodegradable tube. As the tube degrades, a blood vessel forms. The study, conducted on mice, could have implications for the treatment of babies and children born with a single ventricle anomaly - a life-threatening .

The Yale surgeons expanded on an earlier study and human trial conducted in Japan on the use of TEVG as conduits in patients with single ventricles. That study was conducted by researchers from Yale and Tokyo Women’s Medical University. Updated results from the trial were recently published in the Journal of Thoracic and Cardiovascular Surgery. Results of the Japanese study are promising and demonstrate the feasibility and utility of using TEVG in congenital heart surgery. The lead author was Toshiharu Shinoka, M.D., Ph.D., now of Yale School of Medicine and a contributing author on the latest PNAS study.

In the PNAS-published investigation, the Yale researchers set out to understand the underlying mechanism of TEVG formation in mice. The tissue-engineered grafts used in both studies differed from older vascular grafts in a critical way. Researchers developed a method of creating mature, living blood vessels by seeding the individual’s own onto a biodegradable tube, or scaffolding. After only a couple of hours of incubation, surgeons were able to implant the seeded scaffolding into the patient.

“After implantation, the seeded blood marrow cells appeared to transform into living blood vessels, very similar to native blood vessels,” said lead author on the PNAS paper, Christopher K. Breuer, M.D., associate professor of pediatric surgery at Yale School of Medicine. “Because the vessels were made of the patient’s own cells, they are not susceptible to rejection.”

In trying to figure out the mechanism of this transformation, the Yale team initially theorized that the bone marrow cells had simply been incorporated into the existing vascular system, but further investigation showed this was not the case. Breuer says his team was startled to discover what was really taking place. “We realized that the grafts appeared to undergo an inflammatory response due to the infiltration of host monocytes - white blood cells that are part of the body’s immune system. Rapid recruitment of these monocytes has been shown before to be intricately involved in natural blood vessel formation, or arteriogenesis. In other words, inflammation from the immune system response was instigating the creation of new blood vessels.”

In infants born with just one ventricle, the heart cannot adequately supply oxygen to the body. These infants are known as “blue babies” because the lack of sufficient oxygen causes cyanosis, a bluish tinge to the skin. Without surgical intervention, the condition is almost always fatal.

Previous methods of correcting this congenital heart defect have relied upon synthetic grafts which often fail due to thrombosis or clotting of the graft. Because of their artificial composition, they may also require replacement as the child grows.

The Yale team’s advance in understanding why tissue-engineered vascular grafts parallel the natural process of vascular formation may have important implications for the growing field of vascular tissue engineering. Yale pediatric cardiologist Alan Friedman, M.D., said, “The revolutionary possibilities established from this work may help define the future of care that we provide to our patients affected by congenital heart disease. These innovations may well change not only the way we think, but the way we practice.”

Other authors on the PNAS study are Jason D. Roh, Rajendra Sawh-Martinez, Matthew P. Brennan, Steven M. Jay, Lesley Devine, Deepak A. Rao, Tai Yi, Tamar L. Mirensky, Ani Nalbandian, Brooks Udelsman, Narutoshi Hibino, Toshiharu Shinoka, W. Mark Saltzman, Themis R. Kyriakides and Jordan S. Prober of the Interdepartmental Program in Vascular Biology and Therapeutics, and Edward Snyder of the Interdepartmental Program in Vascular Biology and Therapeutics and the Department of Laboratory Medicine, Yale School of Medicine.

Explore further: Mice study shows efficacy of new gene therapy approach for toxin exposures

add to favorites email to friend print save as pdf

Related Stories

Bioengineers create stable networks of blood vessels

Feb 28, 2006

Yale biomedical engineers have created an implantable system that can form and stabilize a functional network of fine blood vessels critical for supporting tissues in the body, according to a report in the ...

Engineered Blood Vessels Function like Native Tissue

Jul 05, 2007

Blood vessels that have been tissue-engineered from bone marrow adult stem cells may in the future serve as a patient's own source of new blood vessels following a coronary bypass or other procedures that require vessel replacement, ...

Genes may predict vascular malformation

Jan 29, 2009

A pair of studies, led by Medical College of Wisconsin scientists at Children's Research Institute in Milwaukee, may translate into rapid molecular tests to distinguish between hemangiomas and congenital blood or lymph vessel ...

Drug can quickly mobilize an army of cells to repair injury

Sep 08, 2006

To speed healing at sites of injury - such as heart muscle after a heart attack or brain tissue after a stroke - doctors would like to be able to hasten the formation of new blood vessels. One promising approach is to "mobilize" ...

Recommended for you

How Alzheimer's peptides shut down cellular powerhouses

Aug 29, 2014

The failing in the work of nerve cells: An international team of researchers led by Prof. Dr. Chris Meisinger from the Institute of Biochemistry and Molecular Biology of the University of Freiburg has discovered ...

User comments : 0