Can tissue engineering mend broken hearts?

Cardiac tissue engineering is an emerging field that may hold great promise for advancing the treatment of heart diseases. Cardiac tissue engineering is in its infancy, and the overall field of tissue engineering, which was formalized in the late 1980s at conferences and workshops sponsored by the National Science Foundation, is still new enough to warrant some description. By broad definition, tissue engineering involves the construction of tissue equivalents through the manipulation and combination of living cells and biomaterials. It is a multidisciplinary field combining diverse aspects of the life sciences, engineering, and clinical medicine. The overall goal of tissue engineering is to develop tissue equivalents for use in the repair, replacement, maintenance, or augmentation of tissues or organs. Although some aspects of cardiac tissue engineering research have been ongoing for generations, albeit without being known as such, directed efforts in the field are only beginning. The main justification for cardiac tissue engineering initiatives is straightforward: congenital and acquired heart diseases are substantial health problems, and there is a limited amount of donor tissue for use in surgical repairs. Heart defects are the most common congenital defect and are the leading cause of death in the first year of life.1,2 Congenital heart defects may occur in as many as 14 of every 1000 live births,3 and approximately 25 000 surgical procedures are performed each year to correct them. Acquired heart diseases also have a profound effect on the population, and despite tremendous advances in medical and surgical treatments, it is estimated that each year 20 000 to 40 000 Americans could benefit from a heart transplant.4 Unfortunately, fewer than 2500 heart transplants are performed each year.4,5 One of the principal reasons for the disparity between patient need and procedures performed is the lack of donor material for implantation. Furthermore, current treatments short of transplantation are essentially restricted to medical and surgical approaches that address the sequelae of the primary defect, and current approaches do not always restore lost structure and/or function. A large number of patients who are not necessarily candidates for transplant may benefit from smaller structures like pieces of muscle, valves, or vessels. There is a need for new approaches to treat profound heart disease, and the possibility that diminished cardiac function may be recovered through the implantation of tissueengineered, biosynthetic constructs is compelling. The need for advanced surgical implant materials is not the only justification for cardiac tissue engineering research, however. The development of tissue equivalents for use in vitro could improve the testing of drugs and potential therapeutic agents and could expand our understanding of cardiac cell biology. Large numbers of animals are used each year in research, drug testing, drug development, pharmacological testing, and education (more than 1.2 million in 1998, excluding rats and mice, according to the USDA). Cell culture alternatives are also routinely used in research and testing; however, typical cell culture models confine cells to a 2-dimensional configuration that does not resemble the organization of cells within the intact tissue. With evidence that cellular activities and responses are affected by organization and mechanical activities,6,7 there is an increasing need to perform studies within the context of the intact cardiac tissue. In addition, the numerous species differences between humans and the animal models used for the research, development, and testing often preclude the use of data derived from animal models to draw specific conclusions about what may happen in humans. The development of human cardiac tissue equivalents would alleviate some of the serious problems associated with species-specific effects. By virtue of being of human origin and organized like tissue, such constructs would provide superior cell culture models for research, reduce the number of animals required for testing, and improve the physiological relevance of in vitro testing. Clearly, the development of either implantable materials or tissue equivalents for use in vitro will require a large amount of concerted effort. Fortunately, substantial groundwork for this effort has been established over the past decades. The first demonstration of in vitro cardiac cell culture was provided by Burrows in the early 1900s.8,9 Ensuing generations of researchers have performed an enormous amount of research using in vitro culture models. Examples of the many contributions in this area include work on extracellular matrix,10,11 studies of 3-dimensional models from suspension culture,12 and details of mechanical force transduction affecting cardiomyocytes.13,14 Each of these may be especially significant to tissue engineers. The application of the wealth of information to potential regenerative therapies has only recently begun. Three general tissue-engineering approaches have been attempted thus far. The first approach involves the implantation of cell suspensions directly into the heart. A number of cell-implantation studies have been performed in animals15–19 and humans20,21 using a variety of cell types. Results from these and related studies demonstrate that implanted cells can incorporate into existing cardiac structures. This approach, The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From the Department of Biomedical Research, A.I. duPont Hospital for Children, Wilmington, Del. Correspondence to Robert E. Akins, PhD, Head of Tissue Engineering and Regenerative Medicine Research, Dept of Biomedical Research, A.I. duPont Hospital for Children, PO Box 269, Wilmington, DE 19899. E-mail [email protected] (Circ Res. 2002;90:120-122.) © 2002 American Heart Association, Inc.