Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches
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Volume
128
Pagination
2949 - 2959
Publisher
Journal
BLOOD
Issue
ISSN
0006-4971
Metadata
Show full item recordAbstract
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. (Blood. 2016;128(25):2949-2959)