Scientific article
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Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

Published inAPL bioengineering, vol. 6, no. 3, 036101
Publication date2022-09
First online date2022-07-08
Abstract

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 3Din vitromodel 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 behaviorin 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.

Keywords
  • Bioengineering
  • Pharmaceuticals
  • Cells
  • Self assembly
  • Tissue engineering
  • Bone marrow
  • Chemotherapy
Citation (ISO format)
GIGER, Sonja et al. Microarrayed human bone marrow organoids for modeling blood stem cell dynamics. In: APL bioengineering, 2022, vol. 6, n° 3, p. 036101. doi: 10.1063/5.0092860
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ISSN of the journal2473-2877
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