Heart transplantation – also called cardiac transplantation – is the treatment of choice for many who suffer severe heart failure. Treatments to prevent infection and suppress the immune system have dramatically increased survival rates, but there simply aren’t enough hearts available.
Nearly 5,000 cardiac transplants occur each year (globally), but there are an estimated 50,000 individuals who qualify for the surgery. This means that only patients with the very worst prognoses will receive a transplant. And there’s always the risk that a person’s body will reject the foreign heart and launch a massive immune attack that can kill the patient. To reduce that risk and eliminate the need for donors, researchers are working to build synthetic hearts from a person’s own cells.
The image above shows regenerated heart tissue maturing in a bioreactor created by scientists at Harvard Medical School and Massachusetts General Hospital. As reported by Popular Science and published in the Circulation Research journal, the team used adult skin cells to grow functional human heart tissue.
“Generating functional cardiac tissue involves meeting several challenges,” says lead study author Jacques Guyette, PhD, of the MGH Center for Regenerative Medicine (CRM). “These include providing a structural scaffold that is able to support cardiac function, a supply of specialized cardiac cells, and a supportive environment in which cells can repopulate the scaffold to form mature tissue capable of handling complex cardiac functions.”
In other words, organs developed in a lab need a sort of ‘scaffolding’ on which to grow – sort of like constructing a house with the frame already in place.
In 2008, research team leader Harald Ott, MD, of the MGH CRM and the Department of Surgery invented a technique in which donor organs are striped with a detergent solution to eliminate certain cells that may incite an immune response from the recipient. The remaining extracellular matrix scaffold is then repopulated with organ-appropriate cells. Ott’s team successfully used the procedure to grow working rat lungs and kidneys before trying it with human hearts.
“This report is the first to conduct a detailed analysis of the matrix scaffold remaining after decellularization of whole human hearts, along with recellularization of the cardiac matrix in three-dimensional and whole-heart formats,” read the study’s press release.
Using 73 donor hearts, the scientists washed away as many cells as possible that were deemed unfit for transplant. Next, researchers used a new technique (involving messenger RNA) to transform adult skin cells into pluripotent stem cells (iPSCs) – cells that can evolve into any type of cell found in the human body. The new cells were ‘instructed’ to differentiate into cardiomyocytes (cardiac muscle cells). The cells were then reseeded into the remaining matrix tissue.
Specialized bioreactor chambers bathed the growing hearts in nutrient solution and provided an environment similar to that of a human body. After two weeks, the hearts contained properly structured tissue that was similar to that of immature human hearts. When given a shock of electricity, the hearts started beating.
This isn’t the first time human heart tissue has been grown in a lab, but it is the closest scientists have ever come to growing a full human heart. But the team admits they aren’t at that level yet.
“Regenerating a whole heart is most certainly a long-term goal that is several years away, so we are currently working on engineering a functional myocardial patch that could replace cardiac tissue damaged due a heart attack or heart failure,” explains Guyette. “Among the next steps that we are pursuing are improving methods to generate even more cardiac cells – recellularizing a whole heart would take tens of billions – optimizing bioreactor-based culture techniques to improve the maturation and function of engineered cardiac tissue, and electronically integrating regenerated tissue to function within the recipient’s heart.”
Editor’s note: This is not strictly speaking a political story, but this under-reported accomplishment is a huge milestone in the advancement of medicine and a celebration of American innovation and ingenuity. Congratulations to these scientists!