Researchers from the University of Pittsburgh School of Medicine report that, for the first time, a mouse heart was able to contract and beat again after its own cells were stripped and replaced with human heart precursor cells. Their work was published on August 13 in Nature Communications.
The scientists believe their study shows the promise that regenerating a functional organ by placing human induced pluripotent stem (iPS) cells in a three-dimensional scaffold could have for transplantation, drug testing models, and understanding heart development.
For the project, the research team first decellularized a mouse heart. Then, they repopulated the remaining heart framework, or scaffold, with multipotential cardiovascular progenitor (MCP) cells. These replacement cells were produced by reverse-engineering fibroblast cells from a small skin biopsy to make iPS cells and then treating the iPS cells with special growth factors to further induce differentiation.
“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,” explained lead investigator Lei Yang, Ph.D., assistant professor of developmental biology at the Pitt 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.”
After a few weeks, the mouse heart had not only been rebuilt with human cells, it also began contracting again, at the rate of 40 to 50 beats per minute, the researchers found. More work must be done to rebuild a heart that will 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, Dr. Yang noted. The model also could be used as a lab-based method to preclinically test the effect of new drugs on the heart or to study how the fetal heart might develop.
“One of our next goals is to see if it’s feasible to make a patch of human heart muscle,” Dr. 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.”