Dealing with rejection

Dr. Taylor’s lab is also experimenting with pig hearts. About the same size as a human heart, extracellular matrix (ECM) “ghost
Dr. Taylor’s lab is also experimenting with pig hearts. About the same size as a human heart, extracellular matrix (ECM) “ghost hearts” like this one have already been produced from pig hearts.
Courtesy The Center for Cardiovascular Repair

Nearly all transplanted organs are subject to some degree of rejection by the recipient’s body. Because a healthy immune system is unable to distinguish between foreign tissues, the recipient’s body attempts to destroy the needed organ just as it would attempt to rid itself of viruses and bacteria.

There are ways to prevent the recipient’s body from rejecting the new organ, but they don’t always work. Sometimes bone marrow can be taken from the organ donor and put into the recipient. The immune cells produced by the new marrow won’t fight the donated organ, but there is a risk that they will start attacking the rest of the host’s body in what is called “graft versus host disease.” Once an organ, or heart, is transplanted, individuals face life-long immunosuppression, often trading heart failure for high blood pressure, diabetes, and kidney failure. Drugs designed to battle this problem don’t work perfectly, and they can have serious side effects if they are required for an extended period of time.

Dr. Taylor’s new process is special in that it could lead to transplantable organs being made out of patients’ own cells. When a freshly grown organ is implanted, the recipient’s body should recognize it as its own tissue instead of rejecting it.

Growing your own heart

Dr. Taylor’s process starts by taking a donor heart and removing all of its original cells. A detergent is pumped through the blood vessels of the heart, bursting and washing away cells. What’s left after all the cells are gone is a pale, squishy heart “skeleton.” Instead of bones, this skeleton is made up of “extracellular matrix,” or ECM. The heart’s ECM is composed of protein fibers that give it structure and act as connective tissue.

Once the cell-less heart is ready, a mix of stem cells and progenitor cells (which are like stem cells, but with less potential to develop into many types of tissue) are injected into the ECM structure, and a solution of oxygen and nutrients is pumped through it. Taylor’s team first tested the process on rat hearts, and in only four days contractions were visible in the developing organs. After eight days, the hearts were beating, and able to pump fluid out the aorta. Gentle electrical signals helped synchronize the contractions throughout the hearts, which continued to beat even after the stimulation was stopped. Some of the hearts were kept beating for a full forty days.

The rat hearts were beating at a small fraction of the power of an adult heart, but Dr. Taylor’s team believes that seeding the ECM with the right mixture of cell types—cells from bone marrow, hearts, and skeletal muscle—will allow optimal growth and strength in the developing organs. The hope is that someday human hearts could be produced this way. Hearts grown on ECM frames would help make up for shortages in donor hearts, and should be indistinguishable to a recipient’s immune system from their original heart.

There’s still a lot of work to be done, but this research could eventually save thousands of lives every year.