Cell therapy for cardiac repair
Imperial College London, National Heart and Lung Institute, Harefield Heart Science Centre, Harefield, UK
British Medical Bulletin 2010; 94: 65–80 DOI:10.1093/bmb/ldq005
Joon Lee and Cesare M. Terracciano
The understanding that a common mechanism of development of heart failure is the loss of ventricular cardiomyocytes leads to the notion of supplementing those losses by delivering cells directly into the diseased ve tricle as a mode of treatment. During the last 15 years, there have been numerous studies performed in the field of cardiac cell therapy involving a wide range of animal models and also in large clinical trials. Some of the reported data have stimulated much interest, and the field continues to be an active area of ongoing research; there has also been considerable controversy over some of the key points and some important questions remain unanswered. In this review, the major recent developments, particularly about the cell types tested in clinical trials, will be summarized, and the outstanding issues discussed.
No meaningful conclusion can be drawn regarding the efficacy in augmentation of function in the injected areas from these early trials. The large randomized controlled trial by Menasche et al.30 measured decreased ventricular luminal dimensions 6 months after skeletal myo- blast transplantation but found no change in ejection fraction. On the other hand, other studies measured clear improvements in ejection frac- tion.28,31 The main limitation of these trials is that their interpretation has been made difficult by concomitant coronary artery surgery, which sometimes included the region receiving myoblast injections. Furthermore, there are differences among studies that make direct comparisons difficult, including differences in cell culture processes (which may influence myoblast viability and differentiation) and the end points used to judge efficacy (including tool of cardiac function assessment), and the variable baseline function of the engrafted regions.
Patient safety has been a concern, especially following the detection of ventricular tachycardia in 4 out of 10 patients in the early study carried out by Menasche et al.26 As a precaution, and also to assess the incidence and timing of graft-related arrhythmias, this group implanted internal cardiac defibrillators in all subsequent patients. In the later study, arrhythmias were detected in 12–17% of patients who received skeletal myoblast transplantation compared with 6% in control patients (P 1⁄4 ns).