A clinical commentary on the articles "strategies for tissue engineering cardiac constructs to affect functional repair following myocardial infarction" and "stem cell-based cardiac tissue engineering" : repairing, reprogramming, and renewing: the promise of myocardial cytotherapeutics.

Heart failure is a major cause of global morbidity and mortality. Over 24 million individuals worldwide have been diagnosed with heart failure with the number of affected individuals projected to approach 20 million by the year 2020 in the USA alone [1–3]. Historically, therapies for heart failure have focused on modulating hemodynamic loading conditions to ameliorate symptoms with salutary effects on cardiac remodeling that improve survival. Surgical advances have also led to improved outcomes after cardiac transplantation; however, the limited number of donor hearts available has driven future therapies into two arenas: biomechanical and biomolecular. The promise of mechanical support devices (MSDs) for end-stage heart failure is being realized; however, this option remains costly and invasive while demonstrating only a limited long-term survival benefit [4]. Furthermore, the long-term impact of device-based ventriculo-vascular coupling remains poorly understood as these devices have altered the overall pattern of circulation to non-pulsatile flow in recipients of MSDs. Over the past two decades, cell-based approaches for heart failure have emerged on a wave of scientific evidence supporting the possibility of generating cells that communicate, conduct, and contract. Two reviews in this edition of the Journal of Cardiovascular Translational Research provide insight into the complexity of cytotherapy from the biomedical engineering perspective. Nunes et al. provide a comprehensive overview of stem cell-based cardiac tissue engineering. Their review highlights the challenges of cell injection and tissue replacement strategies, and then examines the role of embryonic and adult stem cells. As highlighted by their review, one of the major issues facing scientists and physicians in this arena is the ability to accurately gauge improvement in cardiac function after cell therapy. Left ventricular ejection fraction (LVEF) measured by echocardiography or magnetic resonance imaging may not be sensitive enough to detect ultrastructural and physiologic improvements in cardiovascular function. For example, many patients with heart failure and severely impaired LVEF (<30%) continue to lead active lives and demonstrate normal cardiac filling pressures with normal stroke volume. In similar fashion, preclinical and clinical studies of cell-based therapies should extend their evaluation of cardiac function beyond LVEF and begin to examine whether cell strategies impact hemodynamic function as measured by a conductance catheter in the pressure volume loop plane. Notably, a majority of preclinical studies also do not provide data regarding survival outcomes. Since many drug strategies improve survival, demonstrating an incremental benefit of cytotherapy over existing therapies in the heart failure population may prove challenging. In the second review, Ye et al. examine strategies for tissue engineering after myocardial infarction by providing a comprehensive analysis of biomaterials and culture This article is a commentary on the following articles: 10.1007/ s12265-011-9303-1 and 10.1007/s12265-011-9307-x