(151f) Chemically-Defined Generation of Aorta-Gonad-Mesonephros (AGM)-like Hematopoietic Stem and Progenitor Cells from Human Pluripotent Stem Cells

Multipotent self-renewing hematopoietic stem and progenitor cells (HSPCs) regenerate the adult blood system after transplantation, which is a curative therapy for numerous diseases including immune-deficiencies, leukemia, and other cancers. Although substantial effort has been applied to generating de novo HSPCs from human pluripotent stem cells, chemically-defined, serum-free, or feeder cell-free conditions for HSPC derivation have not been reported. Here we describe the development of a defined, albumin and feeder-free culture, with synergistic modulation of Activin and Wnt signaling during the hemato-vascular mesoderm formation, supports the generation of multipotent HSPCs that go through the intermediate aorta-like vessels, similar to hematopoiesis in the aorta-gonad-mesonephros (AGM). Importantly, the resulting cells displayed lymphoid, myeloid and erythroid potential in vitro, and homed to fish caudal hematopoietic tissue (CHT) in vivo after transplantation, mimicking aspects of human AGM hematopoiesis. Our findings provide a significant advance in defining critical components for the induction of homogenous definitive hematopoiesis in vitro. By reducing the complexity of hematopoietic induction, our approach will offer enhanced understanding of human embryonic hematopoiesis and expedite the development of hPSC-derived hematopoietic and immune cell products for therapeutic purpose.