| Autor: |
Sonja Giger, Moritz Hofer, Marijana Miljkovic-Licina, Sylke Hoehnel, Nathalie Brandenberg, Romain Guiet, Martin Ehrbar, Esther Kleiner, Katharina Gegenschatz-Schmid, Thomas Matthes, Matthias P. Lutolf |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
APL Bioengineering, Vol 6, Iss 3, Pp 036101-036101-14 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2473-2877 |
| DOI: |
10.1063/5.0092860 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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