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

人类畸胎瘤衍生的造血是人类脐静脉内皮细胞支持的高度多克隆过程

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作者:Friederike Philipp, Anton Selich, Michael Rothe, Dirk Hoffmann, Susanne Rittinghausen, Michael A Morgan, Denise Klatt, Silke Glage, Stefan Lienenklaus, Vanessa Neuhaus, Katherina Sewald, Armin Braun, Axel Schambach

Abstract

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.

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