Institute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, Germany; Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany.
Institute of Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße1, 30625 Hannover, Germany.
Stem Cell Reports. 2018 Nov 13;11(5):1051-1060. doi: 10.1016/j.stemcr.2018.09.010. Epub 2018 Oct 18.
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.
造血干细胞（HSCs）可确保终生血液系统的再生，因此是移植和基因治疗的重要来源。畸胎瘤环境支持从人类多能干细胞中复杂地发育出功能性 HSCs，这在培养中很难再现。该模型模拟了早期造血的各个方面，但受到自发造血率低的限制。在这项研究中，我们详细阐述了一种可行的造血方案。当在提供人细胞因子的 NSGS 小鼠中生成畸胎瘤时，我们实现了畸胎瘤衍生造血细胞群的显著增加，同时还共同注射了人脐静脉内皮细胞。由于人们对畸胎瘤中的造血知之甚少，因此我们解决了造血谱系的定位和克隆性问题。我们的结果表明，早期人类造血在畸胎瘤形成中得到了很好的体现，因此突出了该模型的价值。
