Rapid cell-growth technique makes pulsing heart tissue

It looks, contracts and responds almost like natural heart muscle—even though it was grown in the lab.

Bioengineered heart muscle, Or BEHM, has been grown into larger patches (above), after starting as a long thin fiber (below). (Photos by Ravi Birla/U-M Artificial Heart Laboratory.)

And it brings scientists another step closer to the goal of creating replacement parts for damaged human hearts, or eventually growing an entirely new heart from just a spoonful of loose heart cells.

University researchers recently reported significant progress in growing bioengineered heart muscle, or BEHM, with organized cells, capable of generating pulsating forces and reacting to stimulation more like real muscle than ever before.

The three-dimensional tissue was grown using an innovative technique that is faster than others that have been tried in recent years, but still yields tissue with significantly better properties. The approach uses a fibrin gel to support rat cardiac cells temporarily, before the fibrin breaks down as the cells organize into tissue.

The U-M team details its achievement in a new paper published online in the Journal of Biomedical Materials Research Part A.

And while BEHM is still years away from use as a human heart treatment, or as a testing ground for new cardiovascular drugs, the researchers say their results should help accelerate progress toward those goals. The University is applying for patent protection on the development and is looking actively for a corporate partner to help bring the technology to market.

Ravi Birla of the Artificial Heart Laboratory in the Section of Cardiac Surgery and the U-M Cardiovascular Center, led the research team.

"Many different approaches to growing heart muscle tissue from cells are being tried around the world, and we're pursuing several avenues in our laboratory," says Birla. "But from these results we can say that utilizing a fibrin hydrogel yields a product that is ready within a few days, that spontaneously organizes and begins to contract with a significant and measurable force, and that responds appropriately to external factors such as calcium."

The new paper actually compares two different ways of using fibrin gel as a basis for creating BEHM: layering on top of the gel, and embedding within it. In the end, the layering approach produced a more cohesive tissue that contracted with more force—a key finding because embedding has been seen as the more promising technique.

The team also assessed the BEHM's structure and function at different stages in its development. First author and postdoctoral fellow Yen-Chih Huang of the Division of Biomedical Engineering, led the creation of the modeling system. Co-author and research associate Luda Khait examined the tissue using special stains that revealed the presence and concentration of the fibrin gel, and of collagen generated by the cells as they organized into tissue.

Over the course of several days, the fibrin broke down as intended, after fulfilling its role as a temporary support for the cells. This may be a key achievement for future use of BEHM as a treatment option, because the tissue could be grown and implanted relatively quickly.

Each approach may turn out to have its own applications, says Birla, and the ability to conduct side-by-side comparisons is important. Other researchers have focused on one approach or another, but the U-M team can use its lab to test multiple approaches at once.