Stem Cell Therapy for Heart Failure

Abstract

Abstract-So far, the major safety issue raised by the use of stem cells for cardiac repair has been the occurrence of ventricular arrhythmias, particularly after skeletal myoblast transplantation. Although one cannot refute a potential intrinsic arrhythmogenicity of stem cells, primarily related to their common lack of electromechanical integration into the recipient myocardium, it is also important to recognize that patients eligible for cell replacement therapy are prone to develop arrhythmias because of their underlying ischemic heart disease. Another confounding factor is the method used for the intramyocardial delivery of the cells, which can cause enough inflammatory tissue damage to further increase ventricular irritability on top of an already high baseline level. Thus any strategy designed to minimize the risk of stem cell-associated ventricular arrhythmias should take into account, besides the cell-specific ability to appropriately couple with host cardiomyocytes, the method of cell transfer and the nature of the myocardial environment targeted for cell engraftment. A more accurate characterization of the baseline risk of arrhythmias in these patients would thus be helpful for better assessing the respective contribution of the donor cells and the host myocardium to these complications. The risk-to-benefit ratio of stem cell therapy will finally have to be revisited in light of the fact that because this baseline risk is usually high, most of these patients will in any way be fitted with an implantable defibrillator. Key Words: arrhythmia Ⅲ cells Ⅲ heart failure Ⅲ myocardial infarction Ⅲ stem cells T he clinical acceptance of any new therapy is largely based on the risk-to-benefit ratio. In the case of stem cell treatment for chronic heart failure, the clinical results have so far been marginally successful, when not negative, whereas the concern that intramyocardial delivery of cells, particularly skeletal myoblasts, could cause potentially life-threatening ventricular arrhythmias has been repeatedly raised. However, in this specific context of heart failure, the legitimate emphasis on this safety issue may have led to somewhat underscore the fact that most of the patients eligible for cell replacement therapy are at high risk of arrhythmias because of their underlying ischemic heart disease to such an extent that they are now increasingly fitted with internal cardioverterdefibrillators (ICDs). 1 The objective of the present article is thus to highlight the fact that the proarrhythmic risk of stem cell therapy may not be entirely related to the cells themselves and to show that at least 2 other factors (ie, the mode of their delivery and the nature of the target substrate) can also be important contributors to posttransplantation arrhythmias. These factors should definitely be taken into account by any strategy aimed at reducing the arrhythmic risk of stem cell therapy. Summary of Experimental Data on StemCell-Induced ArrhythmiasBasically, there are 3 major mechanisms that can cause arrhythmias: reent...

21 Intravenous administration of puppy deciduous teeth stem cells in degenerative valve disease

“…However, understanding the paracrine mechanism of pDSCs for regenerative therapy requires further studies to support our finding. Furthermore, a long-term following up is needed to study the mechanism of cells therapeutic actions [31,32]. As can be observed in our study, improvement in left ventricular systolic function in dogs treated with pDSCs might be due to the paracrine effects.…”

Stem cells in rhythmology — Short communication

“…Now it is also clear that proarrhythmic risk of stem cells may not be exclusively associated to the cells but the cell delivery methods and the nature of target substrate can also be important contributors to arrhythmias following transplantation. The first relevant large-scale randomized clinical trial looking into this was the MAGIC (Myoblast Autologous Grafting in Ischemic Cardiomyopathy) trial which suggested that engraftment of unmodified skeletal myoblasts may generate arrhythmias [13,14]. However, data from more recent large trials show that ventricular arrhythmic events did not differ after intramyocardial injection of skeletal myoblasts or placebo [15].…”

Cardiac Muscle Engineering: Strategies to Deliver Stem Cells to the Damaged Site

“…Such negative results were ascribed to the inability of skeletal myoblasts to balance cell death and achieve complete electromechanical integration with the recipient myocardium. Finally, skeletal myoblast administration was reported to determine no enhancement in major cardiac adverse events and mild effects on left ventricular remodeling process [53,54]. More recently, final results from SEISMIC [Safety and Effects of Implanted (Autologous) Skeletal Myoblasts (MyoCell) Using an Injection Catheter] Trial, a phase II-a study encompassing 40 patients experiencing congestive heart failure and receiving percutaneous intramyocardial injection of autologous skeletal myoblasts, reported the feasibility and safety of this procedure without significant arrhythmogenic events recorded at 6-month follow-up with respect to control groups, although left ventricular ejection fraction did not result significantly improve.…”