title: Versatile humanized niche model enables study of normal and malignant human hematopoiesis.
abstract: The BM niche comprises a tightly controlled microenvironment formed by specific tissue and cells that regulates the behavior of hematopoietic stem cells (HSCs). Here, we have provided a 3D model that is tunable in different BM niche components and useful, both in vitro and in vivo, for studying the maintenance of normal and malignant hematopoiesis. Using scaffolds, we tested the capacity of different stromal cell types to support human HSCs. Scaffolds coated with human mesenchymal stromal cells (hMSCs) proved to be superior in terms of HSC engraftment and long-term maintenance when implanted in vivo. Moreover, we found that hMSC-coated scaffolds can be modulated to form humanized bone tissue, which was also able to support human HSC engraftment. Importantly, hMSC-coated humanized scaffolds were able to support the growth of leukemia patient cells in vivo, including the growth of samples that would not engraft the BM of immunodeficient mice. These results demonstrate that an s.c. implantation approach in a 3D carrier scaffold seeded with stromal cells is an effective in vivo niche model for studying human hematopoiesis. The various niche components of this model can be changed depending on the context to improve the engraftment of nonengrafting acute myeloid leukemia (AML) samples.
authors.forename: Ander
authors.initials: A
authors.lastname: Abarrategi
authors.forename: Katie
authors.initials: K
authors.lastname: Foster
authors.forename: Ashley
authors.initials: A
authors.lastname: Hamilton
authors.forename: Syed A
authors.initials: SA
authors.lastname: Mian
authors.forename: Diana
authors.initials: D
authors.lastname: Passaro
authors.forename: John
authors.initials: J
authors.lastname: Gribben
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mufti
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
mesh_terms: D000818:Animals; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D055153:Stem Cell Niche / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*