Methods for generating serum-free and/or xenogen-free cardiac explant-derivedstem cells(EDC) are provided. These methods may comprise steps of providing an initialcardiac explant,which has been minced and digested; plating the initial cardiac explant;culturing the platedcardic explant in serum-free and xenogen-free medium; harvesting EDC cellssurrounding oremerging from the plated cardiac explant; and optionally performing staticexpansion ofharvested EDC cells in serum-free and xenogen-free media. Serum-free and/orxenogen-freecardiac EDC cells produced by these methods, as well as methods and usesthereof for thetreatment of heart failure in a subject in need thereof, are also provided.
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