Microarrayed human bone marrow organoids for modeling blood stem cell dynamics

被引:24
作者
Giger, Sonja [1 ]
Hofer, Moritz [1 ]
Miljkovic-Licina, Marijana [2 ]
Hoehnel, Sylke [3 ]
Brandenberg, Nathalie [1 ]
Guiet, Romain [1 ]
Ehrbar, Martin [4 ]
Kleiner, Esther [4 ]
Gegenschatz-Schmid, Katharina [4 ]
Matthes, Thomas [2 ]
Lutolf, Matthias P. [1 ]
机构
[1] Ecole Polytech Fed Lausanne, Lab Stem Cell Bioengn, Lausanne, Switzerland
[2] Geneva Univ Hosp, Dept Oncol, Hematol Serv, Geneva, Switzerland
[3] EPFL Innovat Pk, SUN Biosci, Lausanne, Switzerland
[4] Univ Hosp Zurich, Ehrbar Lab, Zurich, Switzerland
关键词
IN-VITRO; NICHE; QUIESCENCE; MICE; ENGRAFTMENT; ENDOSTEAL; ALLOWS;
D O I
10.1063/5.0092860
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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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页数:14
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