Myocardial cell sheet therapy and cardiac function.

Heart failure (HF) is the leading cause of death in developed countries. Regenerative medicine has the potential to drastically improve treatment for advanced HF. Stem cell-based medicine has received attention as a promising candidate therapy over the past decade; however, it has not yet realized this potential in terms of reliability. The cell sheet is an innovative technology for constructing aligned graft cells, and several cell sources have been investigated for making a feasible cell sheet. The most representative thus far is skeletal myoblast, although such cells raise the issue of arrhythmogenicity. Regenerative cardiomyocytes (CMs) derived from pluripotent stem cells (PSCs), such as embryonic stem cells or induced PSCs, are the most promising, because a myocardial cell sheet (MCS) constructed with regenerative CMs can potentially enable contraction recovery and electromechanical coupling with host CMs. The functional outcomes of experimental MCS are reduction of ventricular wall stress and paracrine effects rather than contraction recovery. Several technical obstacles still hamper the clinical application of MCSs, with graft survival the most pivotal issue. Ischemia, apoptosis, inflammation, and immune response can all cause graft cell death, and a stable blood supply to the MCS is critical for successful engraftment. Ventricular tachycardia must also be considered in any myocardial cell therapy, and multiple layering of MCS (>3 layers) is necessary to reconstruct human myocardium. Innervation is also a potential issue. The future application of myocardial cell therapy with MCS for advanced HF depends on resolving these difficulties.