Cytoprotection and Preconditioning for Stem Cell Therapy

Abstract

Coronary heart disease is the leading cause of morbidity and mortality worldwide. To date, management of myocardial infarction (MI) has been limited to timely revascularization and drug therapy aimed to restore coronary blood flow and to reduce myocardial workload. When disease progresses to life-threatening end-stage heart failure, heart transplantation is the only effective therapeutic option available. However, its usage is very much restricted by the severe shortage of heart donors and the complications associated with enduring immune suppressive drug treatments (Miniati & Robbins, 2002). Therefore, innovative treatment strategies are clearly needed to improve patient outcomes. Recent advances in stem cell medicine have shed new light on potential MI therapies by exploiting the pluripotency of stem cells for cardiac repair and regeneration. Although immense progress has been made on the choice of cells and optimizing transplantation conditions, these remain critical issues when translating into the clinical setting of MI. In particular, poor survival of transplanted cells in the hostile microenvironment of the ischaemic myocardium and hence lack of significant engraftment in the heart has been a major impediment for achieving an effective stem cell therapy for MI (Pagani et al., 2003). Various cytoprotection strategies have been developed over the past decade to circumvent this limitation and the non-genetic approach of preconditioning has emerged as one of the most promising clinically adaptable strategies to promote stem cell survival and function under various ischaemic conditions. Although genetic enhancement of stem cells has been very successful in pre-clinical studies, the technical complexity and safety concerns (oncogenicity and mutagenesis) associated with this alternative approach have precluded its application in clinical translation (Bonaros et al., 2008; Penn & Mangi, 2008). This review will focus on current pre-clinical development of non-genetic preconditioning approaches to improve the therapeutic potential of stem and progenitor cells for repair of the heart after MI.