Over the past 2 decades, there have been numerous stem cell studies focused on 
cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series 
of papers focuses on the legacy of these studies and the outlook for future 
treatment of cardiac diseases with stem cell therapies. The first section by 
Drs. Rosen and Myerburg is an independent review that analyzes the basic science 
and translational strategies supporting the rapid advance of stem cell 
technology to the clinic, the philosophies behind them, trial designs, and means 
for going forward that may impact favorably on progress. The second and third 
sections were collected as responses to the initial section of this review. The 
commentary by Drs. Francis and Cole discusses the review by Drs. Rosen and 
Myerburg and details how trial outcomes can be affected by noise, poor trial 
design (particularly the absence of blinding), and normal human tendencies 
toward optimism and denial. The final, independent paper by Dr. Marbán takes a 
different perspective concerning the potential for positive impact of stem cell 
research applied to heart disease and future prospects for its clinical 
application. (Compiled by the JACC editors).