Safety Aspects of Stem Cell Therapy for Ischemic Heart Disease
Preclinical trials using stem cell therapy for treatment of cardiovascular diseases continue to be conducted, with the hope of improving therapeutic efficacy and prolonging patient survival. However, potential safety concerns remain an overriding priority in these clinical trials. Results to date, in regard to safety, have been encouraging. Many studies have provided evidence that autologous stem cells are safe and feasible platforms to treat ischemic myocardial ischemia.
The safety of these clinical trials is evaluated by assessing major cardiac adverse events (MCAE). An MCAE is defined as the composite of cardiovascular- and noncardiovascular-related deaths, myocardial infarctions, congestive heart failures, resuscitated sudden deaths, stroke, and arrhythmias (Menasche et al. 2008). Other events that are evaluated as well are oncogenic transformation, multi-organ seeding, aberrant cell differentiation, and accelerated atherosclerosis (Gersh et al. 2009). Recent studies using BMSCs provide reassurance about the long-term safety of intramyocardial (Leistner et al. 2011; Strauer et al. 2001), epicardial (Stamm et al. 2003), and endocardial (Tse et al. 2003) cell therapy in humans with severe heart failure.
Cell therapy for heart diseases is still in its infancy and requires thorough evaluation of both short- and long-term complications of the therapy. Previous studies have reported that prolonged culture of human embryonic stem cells (hESCs) may lead to structural and chromosomal abnormalities as well as variations in DNA copy number during cultivation (Maitra et al. 2005; Narva et al. 2010). Moreover, it is difficult for iPSCs to maintain genomic stability during reprogramming (Laurent et al. 2011). Therefore, to date, the applications of hESCs and iPSCs in clinical trials have been limited. For MSCs, Wang et al. have demonstrated that majority of cultured hUC-MSCs develop genomic alterations but do not undergo malignant transformation. Despite this, management of genomic stability is recommended before these cells are used for clinical applications (Wang et al. 2013).
Several earlier studies have documented malignant ventricular arrhythmias after skeletal myoblast transplant. Inherent electrophysiological properties of myoblasts differ from stem cells; their ability to couple electromechanically among themselves or with host cardiomyocytes is not the same (Makkar et al. 2003). Clinical data derived from BMSC-based therapy for heart disease has been suggested that stem cell transplantation is less likely to cause arrhythmias than myoblast transplantation (Schachinger et al. 2004; Stamm et al. 2003; Strauer et al. 2001).