Establishing human leukemia xenograft mouse models by implanting human bone marrow-2 like scaffold-based niches
MetadataShow full item record
In order to begin to understand 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 (MSCs) into immune deficient mice we 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 covering all important genetic and risk subgroups. We find that by providing a humanized environment stem cell self-renewal properties are better maintained as determined by serial transplantation assays and genome-wide transcriptome studies, and less clonal drift is 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.