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Versatile humanized niche model enables study of normal and malignant human hematopoiesis

Abarrategi, A; Foster, K; Hamilton, A; Mian, SA; Passaro, D; Gribben, J; Mufti, G; (2017) Versatile humanized niche model enables study of normal and malignant human hematopoiesis. Journal of Clinical Investigation , 127 (2) pp. 543-548. 10.1172/JCI89364. Green open access

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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.

Type: Article
Title: Versatile humanized niche model enables study of normal and malignant human hematopoiesis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/JCI89364
Publisher version: https://doi.org/10.1172/JCI89364
Language: English
Additional information: This is the published version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Animals, Hematopoiesis, Hematopoietic Stem Cells, Humans, Leukemia, Myeloid, Acute, Mesenchymal Stromal Cells, Mice, Models, Biological, Stem Cell Niche, Tumor Microenvironment
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10045565
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