Cardiac Tissue Engineering

Investigators:

• Robert E. Akins, PhD
• Christian Pizarro, MD

Background

A significant number of children are born with cardiac malformations, and about 25,000 children per year undergo some type of corrective surgery for congenital heart defects. In addition, children with certain types of infectious or acquired diseases lose cardiac function when portions of the heart are damaged. Experience has shown that the heart has a limited ability to repair itself. Surgical and/or medical management are usually required to treat patients with severe cardiac problems, and treatments for both structural and functional problems have become highly advanced, but, when they fail, whole organ replacement remains the only other option. At present, heart transplantation is limited by both the number of donors and by the limited life-span of implanted organs.

What We're Doing

We are working toward the development of tissue-engineered cardiac replacements for use in the repair of congenitally under-developed or damaged tissue. Our current research efforts are designed to investigate the cellular organization of the heart and to study how aspects of this organization can be re-established in culture using specialized bioreactors. To do this, we are using a combination of cell biological, molecular, and surgical approaches. The photograph above shows human cardiac cells that were collected from tissue donated by a patient. The cells have been stained with three different fluorescent markers. Blue indicates the nuclei of two adjacent cells, green indicates a protein called vimentin, and red indicates filaments of a protein called actin. Actin filaments are important in the contraction of the heart. The predominantly red cell with the "cross-striated" pattern seen here is a cardiac muscle cell. It has been grown in close association with other cardiac cells, which are predominantly green. We use fluorescent labeling like this to quantitate the amount of each protein and to identify cells of a particular type in our cultures.

Some of What We've Found

We have found that isolated cardiac cells can regenerate aspects of the three-dimensional architecture seen in the heart. We think that it may be possible to take advantage of this intrinsic organizational ability to construct cardiac tissue equivalents in the lab. Although there is a large amount of work that needs to be done, we hope that cardiac tissue engineering will provide a source of implantable material for surgeons to use in the treatment of congenital and acquired diseases of the heart. In the long run, we hope to improve our understanding of the basic cell biology associated with cardiac structure and to increase the number of patients that can be treated for a host of heart diseases.