Heart transplants have given new life to thousands, but are only an unfulfilled hope to thousands more due to a shortage of donor organs. With the goal of meeting this shortfall, scientists at the University of Pittsburgh School of Medicine have bioengineered a mouse heart in the lab that beats on its own. The mouse heart had its cells replaced with human cells, offering the potential of growing custom replacement hearts that wouldn't be rejected by the recipient.
Over 3,500 heart transplants are performed annually worldwide, but that figure pales in comparison to the some 800,000 people who suffer from heart defects so severe that a new organ is needed. Not only are donated hearts in short supply, but there are all sorts of logistical problems involved in transplanted donated hearts. Worse, a heart transplant, no matter how carefully selected for compatibility, involves placing foreign tissues in someone’s chest, which the recipient’s body will fight to destroy. This means a lifetime of immunosuppressant drugs followed by more drugs to fight off infections.
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The University of Pittsburgh approach is based on a technique already used recently in an experiment to build a functioning rat kidney. In a sense, it’s like stripping a car down to its chassis and then rebuilding it. The team started out with a mouse heart that was “decellularized,” which means that it was treated with detergents and other chemicals over a ten-hour period to remove all the cells, leaving behind only a scaffolding of collagen.
This scaffolding is very important because if you try to grow a muscle from some cells, you’ll just end up with a pile of cells. To build a functional heart, it needs a scaffolding like the one a natural heart or other organs build as they grow. This way, the heart cells can specialize, fall into the correct places, and function as they should.
The team took the decelluarized mouse heart and replaced the removed cells – only in this case, the cells were human, not mouse. The cells used were multipotential cardiovascular progenitor (MCP) cells. These are a class of embryonic precursor cells with the power to turn into other kinds of cells under the proper conditions. The scientists produced these by reverse engineering fibroblast cells taken during a biopsy to produce what are called induced pluripotent stem (IPS) cells. When treated with growth factors, they differentiate into the required type of 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,” says senior investigator Dr. Lei Yang. “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.”
The result of the experiment was not only an organ that was structurally a heart, but it worked like one. Within weeks of the precursor cells being introduced, the heart was able to contract and beat at 40 to 50 beats per minute.
The scientists are currently working on a way to make an engineered heart contract with enough strength to pump blood. But a heart doesn't work by itself. It needs regular nerve impulses to act as a pacemaker, so this connection needs to be engineered. According to Dr. Yang, the technique could not only be used for transplants, but also for drug testing and studying heart development.
There’s also the possibility of building a custom heart from a patient’s own tissues to prevent rejection and Dr. Yang says the technique could be used to repair hearts instead of replacing them. “One of our next goals is to see if it’s feasible to make a patch of human heart muscle. 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.”
The results of the research were published in Nature Communications.
Source: University of Pittsburgh