Compositions and methods for improving the functional efficacy of stem cell-derived cardiomyocytes

Abstract

This invention provides an isolated stem cell that has been modified to provide, enhance or contain the functional characteristics of the sarcoplasmic reticulum (SR). The isolated stem cells are modified in one or more of the following manners: by expressing a calcium channel protein; by expressing a calcium pump protein such as the sarcro/endoplasmic reticulum Ca2+-ATPase (SERCA) protein; by inhibiting or downregulating expression of the Na+/Ca+ exchanger (NCX) protein; by expressing a calcium handling protein; by expressing a transverse (t-tubule; and/or by expressing a transverse (t-tubule biogenic protein. After the cell has been modified, it may be expanded to a substantially homogenous population of these cells or alternatively, differentiated to a more mature cell type. Compositions containing these cells and population of cells are also provided by this invention. The cells and compositions can he used to regenerate cardiac tissue, improve cardiac function, restore action potential of cardiac tissue; and treat or prevent cardiac malfunction. These methods can be achieved by administering an effective amount of a cell or population of cells or tissue of this invention to a host in need thereof. The cells and population of cells can be used diagnostically to screen drug or other therapeutic candidates.