The ability to create new cardiac tissue using progenitor cells via engraftment would be a significant advance. However, the existing types of progenitor cells presently in Phase I clinical trials face significant limitations, including lack of evidence that the donor cells (1) produce new cardiac myocytes, versus creating benefits via neoangiogenesis or ventricular remodeling, and (2) establish proper electrical connections to the cardiac tissue after grafting. These limitations are particularly true for bone-marrow derived stem cells and skeletal myoblasts, respectively. To overcome these limitations, Kardia Therapeutics, Inc. seeks to identify and isolate the human equivalent of the murine Sca-1 + adult cardiac progenitor cell for cardiac regeneration. Kardia founding scientists at Baylor College of Medicine discovered the murine Sca-1 + adult cardiac progenitor population, which have been found to be predisposed to cardiac differentiation in vitro and that have proven potential to become cardiac myocytes in vivo. Feasibility has been shown by proof-of-concept studies in a murine model, which show that the Sca-1 + cells home to injured myocardium, engraft without disrupting the normal tissue architecture, and show evidence of spatially appropriate gap junction formation at the points of contact with native heart muscle. In this Phase I STTR application, Kardia seeks to identify the equivalent adult cardiac progenitor cell population in humans. Although the Sca-1 surface marker is not expressed in higher mammals, Kardia believes it is feasible to identify the human Sca-1 + cardiac cell equivalent using its founders' proprietary knowledge of secondary surface markers that are consistent with a mesangioblast-like lineage and other characteristics of the murine Sca-1 + cells. The Specific Aims of the Phase I Research Plan are: 1. Identify and isolate the human equivalent of the murine Sca-1 + adult cardiac progenitor cell, using a combination of surface-expressed and readily assayable internal markers. 2. Perform the initial in vitro characterization of the human Sca-1 + adult cardiac cell equivalent, to demonstrate that the cells are suitable for further evaluation in a subsequent Phase II STTR program. If the Phase I Research Plan is successful, Kardia's Phase II Research Plan will perform the complete in vitro and in vivo functional characterization of the human Sca-1 + adult cardiac cell equivalent in an immunosuppressed mouse model, and later, in a larger mammalian recipient. Ultimately, clinical studies of the regeneration of cardiac tissue in patients with cardiac failure following myocardial infarction will be performed. If successful, this approach will lead to an innovative, therapeutically significant product for myocardial repair.