title: Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches.
abstract: 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.
authors.affiliation: Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Antonella
authors.identifier: 0000-0003-1497-3586
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Department of Hematology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Willy A
authors.initials: WA
authors.lastname: Noort
authors.affiliation: Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Jenny
authors.initials: J
authors.lastname: Jaques
authors.affiliation: Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Bauke
authors.initials: B
authors.lastname: de Boer
authors.affiliation: Department of Hematology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Regina
authors.initials: R
authors.lastname: de Jong-Korlaar
authors.affiliation: Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Annet Z
authors.initials: AZ
authors.lastname: Brouwers-Vos
authors.affiliation: Department of Hematology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Lubbers-Aalders
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jeroen F
authors.initials: JF
authors.lastname: van Velzen
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Andries C
authors.initials: AC
authors.lastname: Bloem
authors.affiliation: Xpand Biotechnology BV, Bilthoven, The Netherlands; and.
authors.forename: Huipin
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Queen Mary University of London, School of Engineering and Materials Science, London, United Kingdom.
authors.forename: Joost D
authors.initials: JD
authors.lastname: de Bruijn
authors.affiliation: Department of Hematology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.affiliation: Department of Hematology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Anton C M
authors.initials: AC
authors.lastname: Martens
authors.affiliation: Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.affiliation: Department of Hematology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: Richard W J
authors.initials: RW
authors.lastname: Groen
authors.affiliation: Department of Experimental Hematology, Cancer Research Center Groningen, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Jan Jacob
authors.initials: JJ
authors.lastname: Schuringa
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D000066673:Cell Self Renewal; D002469:Cell Separation; D002999:Clone Cells; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D010641:Phenotype; D055153:Stem Cell Niche; D017154:Stromal Cells / Q000473:pathology; D054457:Tissue Scaffolds / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays