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B9: Sustained engraftment of limited numbers of human hematopoietic stem cells in mice

Project leader: Prof. Dr. C. Waskow

Understanding human stem cell biology requires in vivo analyses. Improving the efficiency of mouse mutants to support human hematopoietic stem cell (HSC) engraftment and immune responses remains an important aim for the study of human hematopoiesis. In the last funding period we have shown that weakening endogenous mouse HSCs allows for the successful transplantation of human HSCs across species barriers into a novel mouse strain without previous conditioning by irradiation. These immune deficient mice carry a defective Kit receptor rendering endogenous mouse HSCs functionally impaired. We found that the mutant Kit receptor allowed for robust and sustained engraftment of human HSCs after transfer. However, successful engraftment depended on the transfer of relatively high numbers of human HSCs – often a limiting factor in experimental set ups, e.g. after genetic modifications. Further, despite a boost in the generation of mature cells of the myeloid lineage, the development of cells of the adaptive immune system seemed suboptimal in those recipient mice. We hypothesize that the genetic background limits engraftment and differentiation capacities of human HSCs in mice. Therefore, we now aim at characterizing a second novel mouse strain that should combine advantages of a mutant Kit receptor for the long-term engraftment of human HSCs, and the generation of mature cells of the lymphoid and myeloid lineages. 

« January 2020 »

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