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research article

Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Giger, Sonja  
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Hofer, Moritz  
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Miljkovic-Licina, Marijana
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September 1, 2022
Apl Bioengineering

In many leukemia patients, a poor prognosis is attributed either to the development of chemotherapy resistance by leukemic stem cells (LSCs) or to the inefficient engraftment of transplanted hematopoietic stem/progenitor cells (HSPCs) into the bone marrow (BM). Here, we build a 3D in vitro model system of bone marrow organoids (BMOs) that recapitulate several structural and cellular components of native BM. These organoids are formed in a high-throughput manner from the aggregation of endothelial and mesenchymal cells within hydrogel microwells. Accordingly, the mesenchymal compartment shows partial maintenance of its self-renewal and multilineage potential, while endothelial cells self-organize into an interconnected vessel-like network. Intriguingly, such an endothelial compartment enhances the recruitment of HSPCs in a chemokine ligand/receptor-dependent manner, reminiscent of HSPC homing behavior in vivo. Additionally, we also model LSC migration and nesting in BMOs, thus highlighting the potential of this system as a well accessible and scalable preclinical model for candidate drug screening and patient-specific assays. (c) 2022 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Type
research article
DOI
10.1063/5.0092860
Web of Science ID

WOS:000822929100001

Author(s)
Giger, Sonja  
Hofer, Moritz  
Miljkovic-Licina, Marijana
Hoehnel, Sylke
Brandenberg, Nathalie  
Guiet, Romain  
Ehrbar, Martin
Kleiner, Esther
Gegenschatz-Schmid, Katharina
Matthes, Thomas
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Date Issued

2022-09-01

Publisher

AIP Publishing

Published in
Apl Bioengineering
Volume

6

Issue

3

Article Number

036101

Subjects

Engineering, Biomedical

•

Engineering

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in-vitro

•

niche

•

quiescence

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mice

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engraftment

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endosteal

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allows

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

Available on Infoscience
July 18, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/189333
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