Abstract

The ability to revive or regenerate severely injured or failing heart muscle is conceptually very attractive as opposed to the largely compensatory and palliative actions of even the best and newest multi-modal medical therapies.To date, much of the focus of regenerative cardiac therapy has been aimed at introducing new cells in order to add or repopulate functional muscle units. While proof of concept has been largely established, the clinical benefits so far have been quite marginal and the value (benefit/cost) even less. As with any field driven largely by advances in science and technical capabilities, results of one technique may be thought to be largely obsolete by the time they are known.As the fields of molecular and cellular biology, immunology, cell-signaling, genomics and proteomics continue to each expand and integrate, our understanding of cellular and organ function grows, and incremental advances at the therapeutic edge are made. The future is promising and will continue to advance commensurate with the speed of modern scientific discovery.This chapter will serve largely as a review of work to date, and data is organized and presented by type of regenerative strategy (cellular vs acellular). Tables and illustrations are organized to aid the reader in gaining a general synthesis of a large body of complex literature over several decades.

Key Points

• Regenerative medicine strategies are still in their infancy in terms of clinical translation due to challenges with clinical study design, knowledge gaps and practical implementation.
• Cardiosphere derived cells offer an alternative to bone marrow and early clinical application is promising, although studies show mixed results with respect to clinical efficacy.
• The combination of stem cells with left ventricular assisted device implantation is thought to synergize the mechanical offloading and cardiac remodeling with anti-fibrotic nature of stem cells. Limited clinical trials have demonstrated safety, but have yet to show efficacy.
• Great strides have been made in the clinical translation of gene therapy for chronic heart failure with many trials currently enrolling; early clinical results demonstrate safety with little therapeutic response.
• Integration of innovations in basic cardiovascular biology paired with lessons from early clinical experiences will allow for optimization regenerative approach and clinical trial design.