Optimizing CD34+ cell doses for large-scale translational, single donor humanized mouse experiments
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Humanized mice are a powerful tool in preclinical assessment of novel therapeutics. However, generation of large homogenous cohorts is believed to be hampered by the limited number of human stem cells retrievable from individual donors, like from umbilical cord blood specimens. Here, we present a streamlined CD34+ cell isolation method that improves yield and purity compared to standard isolation protocols, enabling more efficient use of umbilical cord blood donations. Enriched CD34+ stem cell preparations yield robust humanization of NSG-SGM3 mice, even with very low input doses, down to a few thousand cells. Using our findings to effectively humanize large cohorts of mice (in this study up to 30 mice from a single stem cell donor), we resolve differences in cytokine release syndrome for two different CAR-T cell products within single-donor settings. These optimizations facilitate larger or smaller humanization experiments, with reduced economical and logistical burden for critical translational research.
