Establishing human leukemia xenograft mouse models by implanting human bone marrow–like scaffold-based niches

Antonella Antonelli, Willy A. Noort, Jenny Jaques, Bauke de Boer, Regina de Jong-Korlaar, Annet Z. Brouwers-Vos, Linda Lubbers-Aalders, Jeroen F. van Velzen, Andries C. Bloem, Huipin Yuan, Joost D. de Bruijn, Gert J. Ossenkoppele, Anton C. M. Martens, Edo Vellenga, Richard W. J. Groen and Jan Jacob Schuringa

Key Points

  • Humanized niche xenograft mouse models were generated that enabled engraftment of patients’ leukemia cells covering all risk groups.

  • Self-renewal was better maintained in the humanized niches as determined by serial transplantation and genome-wide transcriptome studies.

Publisher's Note: There is an Inside Blood Commentary on this article in this issue.


To begin to understand the mechanisms that regulate self-renewal, differentiation, and transformation of human hematopoietic stem cells or to evaluate the efficacy of novel treatment modalities, stem cells need to be studied in their own species-specific microenvironment. By implanting ceramic scaffolds coated with human mesenchymal stromal cells into immune-deficient mice, we were able to mimic the human bone marrow niche. Thus, we have established a human leukemia xenograft mouse model in which a large cohort of patient samples successfully engrafted, which covered all of the important genetic and risk subgroups. We found that by providing a humanized environment, stem cell self-renewal properties were better maintained as determined by serial transplantation assays and genome-wide transcriptome studies, and less clonal drift was observed as determined by exome sequencing. The human leukemia xenograft mouse models that we have established here will serve as an excellent resource for future studies aimed at exploring novel therapeutic approaches.

  • Submitted May 26, 2016.
  • Accepted September 25, 2016.
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