The use of humanized immune system mice in experimental sepsis: a scoping review of reporting and methodology

This scoping review mapped published studies using Humanized Immune System (HIS) mouse models in sepsis research, evaluated reporting completeness against Minimal Information for Standardization of Humanized Mice (MISHUM) and Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS) guidelines, and characterized methodological diversity in HIS mouse generation and sepsis induction. The protocol was registered in PROSPERO. PubMed, Web of Science, and Scopus were searched. Eligible studies were assessed for reporting completeness and methodology related to HIS model generation (MISHUM) and sepsis induction (MQTiPSS). Of 344 identified records, 11 were included. No study reported all key MISHUM parameters; donor age, donor sex, and recipient sex were unreported in > 80% of studies. MQTiPSS assessment revealed universal gaps in treatment blinding and organ dysfunction scoring; well-being monitoring and quantitative organ dysfunction data were absent in 82% of studies, and antimicrobial use data in 55%. Five studies employed hematopoietic cell transplantation (HCT)-humanized NSG mice subjected to CLP, yet substantial heterogeneity was observed in hCD34⁺ cell dose, myeloablative regimens, reconstitution timing, and sepsis induction details. Our findings reveal substantial methodological heterogeneity and critical reporting gaps in HIS sepsis models. This underscores the need for enhanced reporting transparency and tailored guidelines. Addressing these limitations will enable comparative studies capable of evaluating the true translational potential of different HIS systems.