PT  - JOURNAL ARTICLE
AU  - Sonja Giger
AU  - Moritz Hofer
AU  - Marijana Miljkovic-Licina
AU  - Sylke Hoehnel
AU  - Nathalie Brandenberg
AU  - Romain Guiet
AU  - Martin Ehrbar
AU  - Esther Kleiner
AU  - Katharina Gegenschatz
AU  - Thomas Matthes
AU  - Matthias P. Lutolf
TI  - Microarrayed human bone marrow organoids for modeling blood stem cell dynamics
AID  - 10.1101/2021.05.26.445803
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.26.445803
4099  - http://biorxiv.org/content/early/2021/05/27/2021.05.26.445803.short
4100  - http://biorxiv.org/content/early/2021/05/27/2021.05.26.445803.full
AB  - 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 a vascular 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.Competing Interest StatementThe authors have declared no competing interest.