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Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging

Passaro, D; Abarrategi, A; Foster, K; Ariza-McNaughton, L; Bonnet, D; (2017) Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging. Journal of Visualized Experiments , 126 , Article e55914. 10.3791/55914. Green open access

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Abstract

Human hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche, an intricate, multifactorial network of components producing cytokines, growth factors, and extracellular matrix. The ability of HSCs to remain quiescent, self-renew or differentiate, and acquire mutations and become malignant depends upon the complex interactions they establish with different stromal components. To observe the crosstalk between human HSCs and the human BM niche in physiological and pathological conditions, we designed a protocol to ectopically model and image a humanized BM niche in immunodeficient mice. We show that the use of different cellular components allows for the formation of humanized structures and the opportunity to sustain long-term human hematopoietic engraftment. Using two-photon microscopy, we can live-image these structures in situ at the single-cell resolution, providing a powerful new tool for the functional characterization of the human BM microenvironment and its role in regulating normal and malignant hematopoiesis.

Type: Article
Title: Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.3791/55914
Publisher version: http://dx.doi.org/10.3791/55914
Language: English
Additional information: Copyright © 2017 Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/).
Keywords: Live imaging, two-photon microscopy, bone marrow, stroma, microenvironment, humanized niche, human hematopoietic stem cells, human leukemia, vasculature, endothelial cells, mesenchymal stromal cells, BMP2
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/10045375
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