Scientists using human stem cells have rebuilt a working mouse heart after stripping it of all of its original cells.
A team of researchers at the University of Pittsburgh’s School of Medicine
first removed all of the cells from a mouse heart, a process they say takes 10 hours. The remaining “scaffold” of the heart was then repopulated with human-induced pluripotent stem (iPS) cells. The iPS cells were made into multipotential cardiovascular progenitor (MCP) cells. The iPS cells were harvested from fibroblast cells from a small human skin biopsy.
“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,” said senior researcher Lei Yang, assistant professor of developmental biology at the Pittsburgh School of Medicine. “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.”
Promising first step
The newly rebuilt heart began to beat at a rate of 40 to 50 beats per minute within a few weeks, the researchers said. While promising, they say more work must be done “to make the heart contract strongly enough to be able to pump blood effectively, and to rebuild the heart’s electrical conduction system correctly so that the heart rate speeds up and slows down appropriately.”
In the future, it might be possible to take a simple skin biopsy from a patient to derive personalized MCPs that can be used to seed a biologic scaffold and regenerate a replacement organ suitable for transplantation, Yang said.
“One of our next goals is to see if it’s feasible to make a patch of human heart muscle,” he 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.”
In the United States, one person dies of heart disease every 34 seconds, and more than 5 million people suffer from heart failure, meaning a reduced ability to pump blood, said Yang.
“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.”
The findings were published in Nature Communications