Heart patches are one manifestation of the tissue engineering approach to regenerative medicine. Cells delivered to the patient are usually combined with a biodegradable scaffold material that provides support to help the cells survive and undertake beneficial signaling actions. A heart patch is some amount of this combined material applied to the exterior of the heart, in some cases simply by injection since the scaffold can be made to be a viscous fluid. The researchers here claim better results by abandoning the scaffolds, however, and implanting thin sheets of engineered cells. This paper reports on the results of an early human trial:
Heart failure, caused primarily by ischemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM), is life-threatening even with excellent treatment. We developed a cell-sheet implantation method that can heal severely damaged myocardium through cytokine paracrine effects, as evidenced by several experiments using infarction or DCM models in both large and small animals. Cell-sheet implants are reported to offer better functional recovery than needle-injection methods, mainly by cytokine paracrine effects despite poor cell survival. Based on these findings from preclinical work, we previously conducted a First-in-Man Clinical Trial using cell-sheet implants. In the present study, we introduced cell-sheet implants to treat cardiomyopathy patients in a Phase I clinical trial to determine the safety, feasibility, and potential effectiveness of cell-sheet implants as a sole therapy.
Fifteen ischemic cardiomyopathy patients and 12 patients with dilated cardiomyopathy, who were in New York Heart Association functional class II or III and had been treated with the maximum medical and/or interventional therapies available, were enrolled. Scaffold-free cell sheets derived from autologous muscle were transplanted over the left ventricle free wall via left thoracotomy, without additional interventional treatments. There were no procedure-related major complications during follow-up. The majority of the ischemic cardiomyopathy patients showed marked symptomatic improvement in New York Heart Association classification and the Six-Minute Walk Test with significant reduction of serum brain natriuretic peptide level, pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vein resistance, and left ventricular wall stress after transplantation instead of limited efficacy in dilated cardiomyopathy patients.
This Phase I study found cell-sheet transplantation as a sole therapy to be a feasible treatment for cardiomyopathy. The promising results in the safety and functional recovery seen in this study warrant further clinical follow-up and larger studies to confirm the therapeutic efficacy of autologous skeletal stem-cell sheets for severe congestive heart failure.