The most radical treatment currently available for severe heart failure is heart transplantation; however, the number of donor hearts is limited. A better approach is to make human cardiac tissues. We developed an original cell sheet-based tissue-engineering technology to fabricate human cardiac tissue by layering myocardial cell sheets. Human induced pluripotent stem (iPS) cells were differentiated into cardiomyocytes to fabricate cardiomyocyte sheets. Initially, three-layer human iPS cardiomyocyte (hiPSCM) sheets were transplanted on subcutaneous tissues of nude rats. Next, to fabricate thicker tissue, three-layer sheets were transplanted on one day, then additional three-layer sheets were transplanted onto them the following day, after the first sheets were vascularized. On day 3, the final three-layer sheets were again transplanted, creating a nine-layer graft (multi-step transplantation procedure). In the last step, six-layer sheets were transplanted on fat tissues of the inguinal portion, which were subsequently resected together with the femoral arteries and veins to make transplantable grafts with connectable vessels. They were then transplanted ectopically to the neck portion of other rats by anastomosing vessels with the host's jugular arteries and veins. Transplanted three-layer hiPSCMs were beating and, histologically, showed a cardiac muscle-like structure with vascular systems. Moreover, transplanted hiPSCMs proliferated and matured in vivo. Significantly thicker tissues were fabricated by a multi-step transplantation procedure. The ectopically transplanted graft survived and continued to beat. We succeeded in fabricating functional human cardiac tissue with cell sheet technology. Transplanting this cardiac tissue may become a new treatment option for severe heart failure. Copyright © 2015 John Wiley & Sons, Ltd.

A 46-year-old man had undergone aortic valve replacement for aortic regurgitation due to active infective endocarditis in 2006. He had been followed by transthoracic echocardiography revealing results within normal limits except for a subannular depressed scar. In 2010, a giant left ventricular pseudoaneurysm was detected on three-dimensional computed tomography. We performed surgery for patch closure of the pseudoaneurysm and redo aortic valve replacement.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by right ventricular enlargement, right heart failure (HF), and ventricular arrhythmias which lead to sudden death especially in young adults. Current recommendations for management of patients with ARVC are antiarrhythmic medications, catheter ablation, and implantable cardioverter defibrillator therapy to prevent sudden cardiac death. However, despite these treatments, few patients suffer from recurrent ventricular arrhythmias or HF unresponsive to conventional management. Heart transplantation (HTx) is a preferred treatment for these cases, but because of a persistent donor heart shortage in Japan, ventricular assist device (VAD) support has become an important option for a management of the end‐stage ARVC. Previous articles reported 4 cases of a successful management by left ventricular assist device (LVAD), but the longest interval of LVAD support was only 333 days. We present 3 cases of ARVC patients who were successfully managed by LVAD implantation for more than a year. These 3 cases are unconventional examples of ARVC patients, considering the nature of the disease. The novelty of these cases should be taken in the context of the extremely long waiting period for HTx in Japan.

Background: The development of regenerative medicine in recent years has been remarkable as tissue engineering technology and stem cell research have advanced. The ultimate goal of regenerative medicine is to fabricate human organs artificially. If fabricated organs can be transplanted medically, it will be the innovative treatment of diseases for which only donor organ transplantation is the definitive therapeutic method at present. Summary: Our group has reported successful fabrication of thick functional myocardial tissue in vivo and in vitro by using cell sheet engineering technology which requires no scaffolds. Thick myocardial tissue can be fabricated by stacking cardiomyocyte sheets on the vascular bed every 24 h, so that a vascular network can be formed within the myocardial graft. We call this procedure a multi-step transplantation procedure. After human-induced pluripotent stem cells were discovered and human cardiomyocytes became available, a thick, macroscopically pulsate human myocardial tissue was successfully constructed by using a multi-step transplantation procedure. Furthermore, our group succeeded in fabricating functional human myocardial tissue which can generate pressure. Here, we present our way of fabricating human myocardial tissue by means of cell sheet engineering technology. Key Messages: Our group succeeded in fabricating thick, functional human myocardium which can generate pulse pressure. However, there are still a few problems to be solved until clinically functional human cardiac tissue or a whole heart can be fabricated. Research on myocardial regeneration progresses at such a pace that we believe the products of this research will save many lives in the near future.