Abstract: The present invention provides a method of inducing mesoderm derived cells from pluripotent stem cells. In contrast to methods known in the art that are often designed to replicate in vivo events of mesoderm induction, the present invention provides a unique, yet simple, method whereby pluripotent stem cells are mesodermally primed in the presence of factors that concomitantly inhibit the spontaneous differentiation of endoderm and ectoderm during expansion and suspension steps. Exposure and/or adherence of primed aggregates to a extracellular matrix that promotes the commitment and survival of induced mesoderm progenitors, followed by exposure to various mesoderm associated factors, allows for the subsequent induction of such cells into terminally differentiated lineages, such as cardiomyocytes. End products of this induction system will ultimately provide an unlimited source of mesoderm-derived cell types for therapeutic and pharmacological purposes.

Abstract: A method to induce ES cells to the cardiac phenotype is disclosed whereby avian precardiac endoderm used as feeder/inducer cells induce high percentage conversion of mouse embryonic stem (mES) cells into cardiac myocytes. Upon induction, the majority (˜65%) of co-cultured ES cell-derived embryoid bodies (EBs) become enriched in cardiac myocytes and exhibit rhythmic contractions. When precardiac mesoderm is included with the precardiac endoderm, ˜100% of EBs become rhythmically contractile. The inductive effect of the precardiac endoderm/mesoderm is mimicked by medium conditioned by these cells. Within each EB induced by medium conditioned by precardiac endoderm/mesoderm, over 80% of the cells become cardiac myocytes.