Patch Helps Heart Tissue to Heal Itself

A novel cell therapy to treat myocardial infarction (i.e., heart damage that follows a heart attack) has been developed by engineers at Columbia Univ. The researchers, led by biomedical engineering professor Gordana Vunjak-Novakovic, successfully combined human stem cells conditioned during in vitro culture to maximize their ability to improve blood flow to the infarcted tissue using a biological composite scaffold designed to deliver these cells to the damaged heart. The scaffold keeps the cells within the infarct bed - in contrast to the massive cell loss associated with infusion of cells alone - and enhances cell survival and function in the infarct bed, where most of the cells would have died because of the obstruction of blood supply.

"This platform is very adaptable, and we believe it could be readily extended to the delivery of other types of human stem cells we are interested in to rebuild the heart muscle and further our research of the mechanisms underlying heart repair," says Vunjak-Novakovic.

To build the platform, the engineers removed the cells of a human heart muscle (the myocardium), leaving a protein scaffold with its composition, architecture and mechanical properties intact. They filled the scaffold with human stem cells and then applied it as a patch to damaged heart tissue. The patch promoted the growth of new blood vessels and released proteins that stimulated the native tissue to repair itself.

The team also used the controllable platform to identify the signaling mechanisms involved in the repair process and the role of cells and scaffold design in heart repair.

Vunjak-Novakovic explains that the approach they developed aims to "instruct" cells to form human tissue by providing them with the right environment. "The cells are the real tissue engineers - we only design their environments so they can do their work. Because these environments need to mimic the native developmental milieu, progress in the field is driven by the interdisciplinary work of bioengineers, stem cell biologists, and clinicians. By enabling regeneration and replacement of our damaged tissues, we can help people live longer and better," she says.

The researchers are investigating the formation of a contractile cardiac patch using human stem cells that can give rise to both the muscle and vascular network of the heart muscle. They are also studying how the cells within such a cardiac patch, when implanted on infarcted heart tissue, develop their ability to generate mechanical force and electrical conduction, and how these functions can be modulated by in vitro culture.

"Ultimately, we envision this system as a possible point-of-care approach, with components produced and assembled in the operating room to most-effectively target signaling mechanisms involved in the repair process of someone's damaged heart," says Vunjak-Novakovic.