Abstract: Described herein are mesenchymal stem cells (MCS) expressing hybrid allosteric receptors (HAR) that are responsive to stromal cell-derived factor 1 alpha (SDF-1?) secreted from acutely infarcted myocardium. Binding of SDF-1? to CXCR4 activates the co-stimulatory signals, bone morphogenetic protein 2 type II receptor (BMP2R2) and BMP type I receptor (ALK3), in order to accelerate the differentiation into cardiomyocytes. HAR-MSC CXCR4 differentiates into cardiomyocytes through Smad1/5 phosphorylation induced by the BMP2 signaling. In acute myocardial infarction (AMI) models, HAR-MSC CXCR4 treatment leads to the functional improvements by facilitated differentiation and increased cytokine secretion. HAR-MSC CXCR4 cells can be used for the treatment of AMI.