Human Teratoma-Derived Hematopoiesis Is a Highly Polyclonal Process Supported by Human Umbilical Vein Endothelial Cells

Abstract

Summary: Hematopoietic stem cells (HSCs) ensure a life-long regeneration of the blood system and are therefore an important source for transplantation and gene therapy. The teratoma environment supports the complex development of functional HSCs from human pluripotent stem cells, which is difficult to recapitulate in culture. This model mimics various aspects of early hematopoiesis, but is restricted by the low spontaneous hematopoiesis rate. In this study, a feasible protocol for robust hematopoiesis has been elaborated. We achieved a significant increase of the teratoma-derived hematopoietic population when teratomas were generated in the NSGS mouse, which provides human cytokines, together with co-injection of human umbilical vein endothelial cells. Since little is known about hematopoiesis in teratomas, we addressed localization and clonality of the hematopoietic lineage. Our results indicate that early human hematopoiesis is closely reflected in teratoma formation, and thus highlight the value of this model. : Schambach and colleagues show evidence that hematopoiesis in hiPSC-derived teratomas occurs by endothelial-to-hematopoietic transition in a highly polyclonal manner. This process was supported by the presence of HUVECs in the NSGS mouse, which provides human SCF, IL-3, and GM-CSF. The established hematopoiesis model can potentially be used for disease modeling and improvement of hematopoietic differentiation protocols. Keywords: hematopoiesis, teratoma, hiPSC, EHT, genetic barcoding, HUVECs, embryogenesis