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May 16, 2008

Biomedical Engineers at Columbia Develop Living Heart Chambers to Aid Study of Cardiac Function

Researchers at Columbia University have developed tiny functioning heart chambers that exhibit the key characteristics of cardiac pumping action. These modified tissue samples, known as organoids, will enable researchers to far more easily study heart growth and development, as well as provide a novel means for evaluating new treatments for diseased or damaged cardiac tissue.

Creating engineered cardiac organoid chambers
Creating Cardiac Organoid Chambers: (A) Inflatable balloon-shaped mold used to create engineered cardiac organoid chambers (scale, mm); (B) Engineered cardiac organoid chamber submerged in growth media during tissue culture before removal of the inner balloon; (C) Spontaneously beating, free-floating organoid chamber after deflation and removal of inner balloon

“We have engineered fully biological, living heart chambers, or organoids, that spontaneously beat and respond to external stimuli,” said Kevin Costa, associate professor of biomedical engineering at the Fu Foundation School of Engineering & Applied Science.

Created under conditions where critical heart functions can be fully monitored and controlled, organoids help researchers clarify the mechanisms governing stem cell differentiation and facilitate the development of therapies for clinical practice. Unlike conventionally engineered cardiac tissue patches, Costa’s organoid offers the unique ability to regulate stress within the organ wall, a key factor influencing cardiac function. It also provides a way to measure the resulting pressure and volume relationships that cardiologists use to define a heart’s pumping capacity.

A description of the research, conducted with doctoral student Eun Jung (Alice) Lee, was published recently in the journal Tissue Engineering.

Scientists studying the heart have traditionally used a century-old technique that involves surgically removing an animal heart and connecting it to electrical stimulators and plumbing to keep it beating and pumping fluid outside of the body. This approach allows for various interventions on how the heart pumps, without the complication of neural regulation, immune responses, and other complexities present in the body.

Columbia Professor Kevin Costa (left) and former doctoral student Eun Jung (Alice) Lee in the Biomedical Engineering laboratory where cardiac organoid chambers were created and tested
Columbia Professor Kevin Costa (left) and former doctoral student Eun Jung (Alice) Lee

A natural heart, however, can only survive a few hours under these conditions, making it difficult to study processes such as development, growth and repair, which take much longer to occur. Computer modeling is another approach biomedical engineers use to study such processes, but, due to the heart’s complex structure and properties, the development of models that can accurately predict changes in heart behavior has proven challenging.

To enable controlled long-term study and facilitate a method to predict heart chamber pump function, Costa and Lee came up with a solution. They engineered special tissues that retained essential physiologic characteristics of the natural heart while allowing for a more simplified theoretical analysis.

“Rather than making the equations more complicated, we wondered if we could make a heart that was less complicated,” Costa said. He and Lee utilized new tissue engineering techniques and a custom inflatable mold to create a three-dimensional, thin-walled spherical cardiac pump out of specialized heart muscle cells embedded in a collagen gel-like material. “The process is kind of like making Jell-O, except it's alive,” Costa said.

The resulting organoid chamber beats on its own, develops pressure, ejects fluid, and exhibits a variety of heart functions never before seen in an engineered cardiac tissue. It also avoids much of the complexity of working with natural hearts, such as the need to maintain a circulatory system to supply oxygen and nutrients.

Costa and his team have also adapted a method to rapidly freeze a targeted portion of the tissue, essentially creating the first engineered organoid heart attack. The ability to create a well-defined injury zone, and then monitor how the healing process evolves and how that affects the pump function of the chamber in a controlled environment, offers an extremely powerful new experimental tool for studying heart disease.