Analysis of parameters that affect human hematopoietic cell outputs in mutant c-kit-immunodeficient mice

作者：Miller Paul H; Rabu Gabrielle; MacAldaz Margarita; Knapp David J H F; Cheung Alice M S; Dhillon Kiran; Nakamichi Naoto; Beer Philip A; Shultz Leonard D; Humphries R Keith; Eaves Connie J^*

来源：Experimental Hematology, 2017, 48: 41-49.

DOI：10.1016/j.ekphem.2016.12.012

Xenograft models are transforming our understanding of the output capabilities of primitive human hematopoietic cells in vivo. However, many variables that affect posttransplantation reconstitution dynamics remain poorly understood. Here, we show that an equivalent level of human chimerism can be regenerated from human CD34(+) cord blood cells transplanted intravenously either with or without additional radiation-inactivated cells into 2- to 6-month-old NOD-Rag1(-/-) -IL2R gamma c(-/-)(NRG) mice given a more radioprotective conditioning regimen than is possible in conventionally used, repair -deficient NOD-Prkdc(scid/scid) -IL2R gamma c(-/-)(NSG) hosts. Comparison of sublethally irradiated and non-irradiated NRG mice and W-41/W-41 derivatives showed superior chimerism in the W-41 -deficient recipients, with some differential effects on different lineage outputs. Consistently superior outputs were observed in female recipients regardless of their genotype, age, or pretransplantation conditioning, with greater differences apparent later after transplantation. These results define key parameters for optimizing the sensitivity and minimizing the intraexperimental variability of human hematopoietic xenografts generated in increasingly supportive immunodeficient host mice.

• 出版日期2017-4