Heart valves calcify over time, and Rice University scientists are beginning to understand why.
The Rice lab of bioengineer Jane Grande-Allen found through studies of pigs’ heart valves that age plays a critical role in the valves’ progressive hardening, and the problem may be due to the infiltration of a protein known as von Willebrand factor (VWF). Tissues from pig valves are commonly used to make human heart-valve replacements.
VWF helps regulate blood clotting in both pigs and humans but, as the Rice team discovered, it finds its way over time into the collagen-rich interior of the valve tissues. Because clotting is not an issue in collagen, there is no apparent need for VWF to be present. The researchers went looking for a connection to the calcium nodules that form in the tissues and make the valves’ leaflets less flexible, which decreases blood flow to the heart.
The new work, detailed in the American Heart Association journal Arteriosclerosis, Thrombosis and Vascular Biology, “opens up a huge line of investigation,” Grande-Allen said.
Jane Grande-Allen has been elected to the Biomedical Engineering Society’s (BMES) Class of 2013 Fellows for her contributions to the field through investigations into the mechanics of heart-valve disease.
Grande-Allen, a professor of bioengineering, joined the Rice faculty in 2003. She directs the Integrative Matrix Mechanics Lab at the BioScience Research Collaborative.
Antibiotic study inspires new pathways in heart-valve research
As people age, or as a result of poor nutrition, heart valves can become damaged by the accumulation of calcium deposits within the tissue. This calcification causes a thickening and hardening of the tissue to the point that it limits normal blood flow.
Bioengineering researchers in Rice Associate Professor Jane Grande-Allen’s laboratory analyze the biomechanics of heart-valve tissue and the underlying cellular and genetic causes of valve disease. One ongoing investigation pursued by her group looks into the roles cellular and matrix components play in normal valve biology and the degenerative processes that can cause the formation of calcified nodules in aortic valve leaflets.
“Very little is known about the intracellular dynamics among genes, proteins and the metabolic pathways that guide either normal processes or give rise to abnormalities,” Grande-Allen said. “Accumulative efforts in our lab involve investigations into valve-cell morphology and disease from a more mechanical perspective. Specifically, we look for cues as to how alterations to cells and cellular environments are driven by mechanical stress of the pumping heart over many years.”
Scientists use magnetic levitation to make in vitro lung tissue more realistic
In a development that could lead to faster and more effective toxicity tests for airborne chemicals, scientists from Rice University and the Rice spinoff company Nano3D Biosciences have used magnetic levitation to grow some of the most realistic lung tissue ever produced in a laboratory.
Scientists from Rice University and the Rice spinoff company Nano3D Biosciences have used magnetic levitation to grow realistic lung tissue in vitro. From left are Glauco Souza, Jacob Gage, Tom Killian, Jane Grande-Allen and Hubert Tseng.
The research is part of an international trend in biomedical engineering to create laboratory techniques for growing tissues that are virtually identical to those found in people’s bodies. In the new study, researchers combined four types of cells to replicate tissue from the wall of the bronchiole deep inside the lung…
…“Growing realistic lung tissues in vitro is a particular challenge,” said study co-author Jane Grande-Allen, professor of bioengineering at Rice. “There are a number of technical obstacles, and scientific funding agencies have placed a particular emphasis on lung tissue because there’s a large potential payoff in terms of reducing costs for pharmaceutical and toxicological testing.”
This year at the 2012 Collaborative Research Awards Luncheon held on Feb. 17, the Virginia and L.E. Simmons Family Foundation provided a total of $635,000 to support the Collaborative Research Fund program. This five-year, $3 million initiative, provides funding to support teams of collaborators from Texas Children’s Hospital, Rice University and The Methodist Hospital Research Institute (TMHRI) as they discover new ways to diagnose and treat diseases.
Of the four projects funded this year, three of the collaborative teams included Texas Children’s Hospital researchers. Successful initial findings will ideally lead the researchers to pursue further funding from the National Science Foundation, the National Institutes of Health and other organizations.
The three team projects with Texas Children’s collaborators include:
• “A stent mounted pulmonary valve targeted to pediatric congenital heart disease:” Dr. Henri Justino from Texas Children’s Heart Center and assistant professor of pediatrics at Baylor College of Medicine (BCM), along with Jane Grande-Allen, Ph.D. and Daniel Harrington, Ph.D. from Rice University were jointly awarded $159,964 to fund their collaborative project. Together, these investigators are developing an artificial valve to repair infant and juvenile hearts that could be inserted into the heart through a catheter to avoid painful, complicated open-heart surgeries. According to the researchers, pulmonary valve replacement surgery now accounts for 75 percent of all valve replacement surgeries in children. Due to poor durability of current replacement valves, repeated surgeries are often necessary; however, a stent-based replacement valve could be inserted using a minimally invasive procedure.
Rice University’s Jane Grande-Allen, one of the world’s foremost experts on the biomechanics of heart-valve tissue, has won an Established Investigator Award from the American Heart Association.
The award, which includes a five-year research grant, recognizes midcareer scientists who have shown “unusual promise and an established record of accomplishments.” Grande-Allen, associate professor of bioengineering and a faculty investigator in Rice’s BioScience Research Collaborative, is the first Rice faculty member to win the award.
“It’s very competitive, in part because there aren’t nearly as many awards for established investigators as there are for people who are just starting out,” Grande-Allen said. “I am completely astounded and delighted that I won it. It’s going to support some of the most exciting research I’ve ever undertaken.”
A team of bioengineers from Rice University is bringing a promising new strategy for growing replacement heart valves closer to reality, thanks to a four-year, $1.2 million grant from the National Institutes of Health. The team hopes to use gel-like materials to generate three-dimensional patterns called scaffolds that can simultaneously mimic the complex structural and physical properties of heart-valve tissues and guide the behavior of tissue-forming cells.
Tissue-engineering researcher Jane Grande-Allen, the lead investigator on the grant, said researchers once believed that replacement heart valves would be one of the easiest and first tissues that could be grown in the laboratory. At just a millimeter thick, the rugged flaps of tissue in heart valves seemed simple enough when researchers first started trying to engineer them in the mid-1990s.
“It’s ironic because they turned out to be one of the most difficult and complex tissues of all,” said Grande-Allen, associate professor in bioengineering at Rice.
Rice University’s Jane Grande-Allen has been selected for the 2011 A.J. Durelli Award by the Society for Experimental Mechanics Inc. (SEM) for her significant innovative contributions of new techniques in experimental mechanics.
The award is given annually to recognize younger members of the society in honor of A.J. Durelli, one of the most outstanding experimental stress analysts in the world during the second half of 20th century. SEM will present Grande-Allen with the award during the society’s annual conference next June in Uncasville, Conn.