Modeling competitive transplantation using HLA-mismatched human hematopoietic stem cells

2026 · doi:10.64898/2026.03.18.712629
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Abstract

Background Competitive transplantation is essential for defining intrinsic repopulating capacity of murine hematopoietic stem and progenitor cells (HSPCs), yet comparable assays for human cells have been limited by the lack of a robust in vivo platform.

Methods

Here, we describe a novel competitive transplantation method in humanized NOD.Cg-KitW-41J Tyr + Prkdcscid Il2rgtm1Wjl/ThomJ (NBSGW) mice that enables simultaneous engraftment and longitudinal tracking of distinct human grafts within a shared microenvironment.

Results

Using human leukocyte antigen-mismatched donor CD34+ cells, this method facilitates standard flow cytometry panels to track multiple donor cell chimerism, lineage output, and HSPC composition. The experimental framework may be adapted to different mouse models, conditioning strategies, donor sources, and treatments.

Conclusions

Overall, this humanized competitive repopulation assay fills a critical translational gap and offers a flexible foundation for advancing mechanistic discovery in human hematopoietic biology and improving clinical strategies for stem cell transplantation. Competing Interest Statement The authors have declared no competing interest. Footnotes Trial Registration: N/A List of abbreviations - BM - bone marrow - CB - Cord blood - HBSS - Hank’s Balanced Salt Solution - HLA - Human Leukocyte Antigen - HSPC - hematopoietic stem and progenitor cell - PB - peripheral blood - PBS - phosphate-buffered saline

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last seen: 2026-05-20T01:45:00.602351+00:00