'Decellularized' Mouse Heart Regenerated with Human Stem Cells

Cells in the heart of a mouse were evacuated and replaced with human stem cells, which later went on to cause the heart regenerate, beat and function somewhat normally in a petri dish, the University of Pittsburgh announced Tuesday.

The breakthrough may lead the way to future developments in heart science that could be used in transplantation, drug testing models and understanding the way the heart develops, which could be a boon for both heart researchers and heart patients.

Senior investigator Lei Yang, Ph.D., an assistant professor of developmental biology at Pitt School of Medicine, reports that every 34 seconds a person dies of heart disease in the U.S. and more than 5 million Americans suffer from heart failure.

Yang contends that he and his colleagues' research, as well as future studies, could lead to more options for heart patients.

"Scientists have been looking to regenerative medicine and tissue engineering approaches to find new solutions for this important problem," Yang said. "The ability to replace a piece of tissue damaged by a heart attack, or perhaps an entire organ, could be very helpful for these patients."

For their study, Yang's team "decellularized" a mouse heart -- a 10-hour process that evacuated the heart of all its cells. Then, the team used pluripotent stem (iPS) cells generated from human skin cells to "repopulate" the decellularized heart framework -- known as a scaffold -- to create precursor heart cells called multipotential cardiovascular progenitor (MCP) cells which later grew into one of three types of functional heart cells.

"This process makes MCPs, which are precursor cells that can further differentiate into three kinds of cells the heart uses, including cardiomyocytes, endothelial cells and smooth muscle cells," Yang explained. "Nobody has tried using these MCPs for heart regeneration before. It turns out that the heart's extracellular matrix -- the material that is the substrate of heart scaffold -- can send signals to guide the MCPs into becoming the specialized cells that are needed for proper heart function."

After a few weeks, the repopulated mouse heart began to contract at the rate of 40-50 beats per minute.

While the research is a breakthrough, more work must be done in order to, among other things, make the heart contract strongly enough to pump blood through a cardiovascular system effectively.

Yang noted that in the future the concept could be used to create personalized heart replacements for patients.

"One of our next goals is to see if it's feasible to make a patch of human heart muscle," Yang added. "We could use patches to replace a region damaged by a heart attack. That might be easier to achieve because it won't require as many cells as a whole human-sized organ would."

Yang and his colleagues' work is published in the journal Nature Communications.