Tissue engineered myoblast sheets improved cardiac function sufficiently to discontinue LVAS in a patient with DCM: report of a case

Abstract

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by progressive heart failure, and is a leading cause of mortality and morbidity. Recently, cellular therapy for end-stage heart failure has been emerging. We herein report a 56-year-old male who received a transplant of autologous myoblast sheets manufactured in temperature-responsive culture dishes. His clinical condition improved markedly, leaving him without any arrhythmia and able to discontinue using a left ventricular assist system and avoid cardiac transplantation. These findings suggest that cellular therapy using myoblast sheets is a promising new strategy for treating patients with end-stage DCM. This method might be an effective alternative to heart transplantation in the near future.

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“…For this reason, we attempted to make small intestinal cell sheets. In previous reports, adhesiveness of cell sheets has proven to have a strong ability to survive within organs as compared with other method of transplantation in vitro [6,41,42]. Cell sheets retained their adhesion molecules consisting of ECM and intercellular adhesion molecules.…”

“…[4] Having such features, cell sheets have been used for ours and a variety of other clinical studies based on new regenerative therapy. Prevention of esophageal stenosis after endoscopic submucosal dissection [5], improvement of heart function against chronic heart dysfunction [6] and improvement of corneal opacity [7] have been performed with human autologous cell sheets as clinical studies in Japan and the outcome in most cases was very favorable.…”

Cell Sheet Tissue Engineering for Heart Failure

“…Based on the promising results in various animal models, there is a clinical study using cell sheet transplantation currently underway. Autologous skeletal myoblast sheet therapy has demonstrated that it is possible to improve cardiac function to such a degree that LVADs are no longer required for patients with dilated cardiomyopathy [20]. …”

Engineering Cardiovascular Regeneration

“…In this study, the transplantation of eight sheets containing 25×10 6 cardiomyocytes improved left ventricular ejection fraction compared to sham (53 vs. 38 %), but the number of human cardiomyocytes remaining on the host myocardium 8 weeks after transplantation was very low, indicating that the functional improvement was independent of new muscle mass and due to a paracrine mechanism, a conclusion similarly made in many cell-therapy studies. After a further study in dogs [108], the group reported the first inman-study, in which cell sheets of autologous skeletal myoblasts were transplanted in a patient with idiopathic DCM and prolonged treatment with a left ventricular assist device [109]. Implantation of the cell sheet was associated with a decrease in brain natriuretic peptide plasma levels (marker of heart failure), increase in left ventricular ejection fraction, and removal of the assist device.…”