Current and future status of stem cell therapy in heart failure.

OPINION STATEMENT: As heart transplantation and mechanical assist technology are inadequate solutions for the growing clinical epidemic of heart failure, myocardial regeneration has moved to the forefront. Multiple laboratories using a variety of cell types have demonstrated myocardial repair in different animal models. Translating these results into clinical practice through clinical trial research has thus far proved challenging. Amassing clinical evidence suggests that cell therapy is safe and offers a modest clinical benefit, but the long-term effect of such therapy as well as the overall impact on the natural progression of heart failure and, ultimately, survival are unknown. Furthermore, cost-benefit analysis of such therapy, which will likely become increasingly important as health care reform takes shape, has not been examined to any degree. Although scientific competition has driven this field with remarkable speed, it is also responsible for its fragmentation, with multiple avenues of pursuit happening in parallel. Consensus opinion is absent with respect to mechanism of action, effectiveness of cell type or delivery method, timing and dosing of cell therapy, adjunctive medication or therapies, and optimum cell type or combination of cell types. Nevertheless, in the arena of clinical medicine, ease of cell availability and cell delivery has proved paramount to cell type selection. The flourish of clinical trials investigating bone marrow-derived stem cells (BMSCs) delivered via direct intracoronary injection testifies to this opinion. The modest improvements in cardiac function demonstrated in trials to date will likely not have a significant clinical impact. We expect, however, that scientific competition will make continued contributions over the next decade that will propel the field forward, resulting in more pronounced clinical benefits in future trials. The authors further believe that the realization of true cardiac regeneration will require the use of autologous cells more capable of retention and differentiation to cardiac cell lineages. We believe that endogenous cardiac progenitor cells have superior regenerative potential to current cell types in this regard. The difficulty in accessing, isolating, and expanding these cells has resulted in less preclinical and clinical interest. Ongoing investigation will better define the capabilities of these cardiac progenitor cells.