A team at Vanderbilt University (Nashville, TN) has made an important discovery regarding the early stages of heart valve formation. W. David Merryman directed the study, which examined the developing hearts of baby chickens to better understand how this key component of the heart is formed.

Eventually, the scientists hope to be able to grow replacement heart valves from a patient's own cells. Existing valves, made of plastic, do not grow with the patient and therefore need to be replaced multiple times in young patients, requiring repeated surgeries. “For the last 15 years, people have been trying to create a heart valve out of artificial tissue using brute-force engineering methods without any success,” explained Merryman in a press release. “We decided to take a step back and study how heart valves develop naturally so we can figure out how to duplicate the process.”

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To do this, first author Mary Kathryn Sewell-Loftin devised a novel culture method for studying the mechanics of developing hearts removed from chick embryos. The U-shaped tube from which a heart develops consists of three layers: the outermost layer is made of cardiac muscle cells, the innermost layer is made of endothelial cells and the middle layer consists of a substance known as cardiac jelly. The cardiac jelly is essential to the process that turns the endothelial cells into valvular interstitial cells, which in turn guide the process of valve formation in the heart. Sewell-Loftin's culture method involved placing the heart in a dish filled with a cardiac jelly facsimile, consisting of collagen gel with a complex sugar called hyaluronic acid added.

Sewell-Loftin also created a computer program to measure the deformations the pulsing of the heart muscle cells created in the gel. The deformation maps showed that areas where there were stronger pulses, and as a result, stronger deformations, were the same areas where more valvular interstitial cells were being formed. This relationship demonstrates that the mechanical forces of the heart muscle on the cardiac jelly are essential for the process underlying the creation of heart valves (Biomaterials 35, 2809–2815; 2014).

“The discovery that the deformations produced by the beating cardiac muscle cells are important provides an entirely new perspective on the process,” Merryman said.

Next, the researchers are collaborating with stem cell scientists to develop the endothelial cells that comprise the inner layer of the embryonic heart. This step may be the missing piece for creating artificial heart valves made of human cells.