Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches
| Autor: | Anton C. M. Martens, Gert J. Ossenkoppele, Willy A. Noort, Jan Jacob Schuringa, Jenny Jaques, Antonella Antonelli, Andries C. Bloem, Annet Z. Brouwers-Vos, Regina de Jong-Korlaar, Joost D. de Bruijn, Jeroen F. van Velzen, Edo Vellenga, Linda Lubbers-Aalders, Huipin Yuan, Richard W.J. Groen, Bauke de Boer |
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| Přispěvatelé: | Stem Cell Aging Leukemia and Lymphoma (SALL), Guided Treatment in Optimal Selected Cancer Patients (GUTS), CCA - Cancer biology, Hematology, Hematology laboratory |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology Myeloid Cell Separation Biochemistry Transcriptome Mice Bone Marrow Cell Self Renewal Stem Cell Niche Tissue Scaffolds Gene Expression Regulation Leukemic Hematology Haematopoiesis Leukemia Leukemia Myeloid Acute medicine.anatomical_structure Phenotype Female EX-VIVO ASSAYS Stem cell STEM-CELLS IMPROVED ENGRAFTMENT medicine.medical_specialty XENOTRANSPLANTATION MODEL Immunology ACUTE MYELOID-LEUKEMIA Biology 03 medical and health sciences LONG-TERM EXPANSION NOD/SCID MICE medicine Animals Humans HUMAN HEMATOPOIETIC-CELLS Gene Expression Profiling Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology medicine.disease Hematopoietic Stem Cells Xenograft Model Antitumor Assays Clone Cells Transplantation SELF-RENEWAL 030104 developmental biology Cancer research Bone marrow Stromal Cells MLL-AF9 LEUKEMIA |
| Zdroj: | Blood, 128(25), 2949-2959. AMER SOC HEMATOLOGY Blood, 128(25), 2949-2959. American Society of Hematology Antonelli, A, Noort, W A, Jaques, J, de Boer, B, de Jong-Korlaar, R, Brouwers-Vos, A Z, Lubbers-Aalders, L, van Velzen, J F, Bloem, A C, Yuan, H, de Bruijn, J D, Ossenkoppele, G J, Martens, A C M, Vellenga, E, Groen, R W J & Schuringa, J J 2016, ' Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches ', Blood, vol. 128, no. 25, pp. 2949-2959 . https://doi.org/10.1182/blood-2016-05-719021, https://doi.org/10.1182/blood-2016-05719021 |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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