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, Jan Jacob Schuringa

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)2949-2959
Number of pages11
Issue number25
Publication statusPublished - 22 Dec 2016

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