Microarrayed human bone marrow organoids for modeling blood stem cell dynamics
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 sys...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
AIP Publishing LLC
2022-09-01
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| Series: | APL Bioengineering |
| Online Access: | http://dx.doi.org/10.1063/5.0092860 |
| _version_ | 1811181247823609856 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Sonja Giger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:15:28Z |
| format | Article |
| id | doaj.art-ede4db85bc1f4ee29ddc191584cc3c49 |
| institution | Directory Open Access Journal |
| issn | 2473-2877 |
| language | English |
| last_indexed | 2024-04-11T09:15:28Z |
| publishDate | 2022-09-01 |
| publisher | AIP Publishing LLC |
| record_format | Article |
| series | APL Bioengineering |
| spelling | doaj.art-ede4db85bc1f4ee29ddc191584cc3c492022-12-22T04:32:23ZengAIP Publishing LLCAPL Bioengineering2473-28772022-09-0163036101036101-1410.1063/5.0092860Microarrayed human bone marrow organoids for modeling blood stem cell dynamicsSonja Giger0Moritz Hofer1Marijana Miljkovic-Licina2Sylke Hoehnel3Nathalie Brandenberg4Romain Guiet5Martin Ehrbar6Esther Kleiner7Katharina Gegenschatz-Schmid8Thomas Matthes9Matthias P. Lutolf10 Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Hematology Service, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland SUN Bioscience, EPFL Innovation Park, Lausanne, Switzerland Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Ehrbar Lab, University Hospital Zurich, Zurich, Switzerland Ehrbar Lab, University Hospital Zurich, Zurich, Switzerland Ehrbar Lab, University Hospital Zurich, Zurich, Switzerland Hematology Service, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland Laboratory of Stem Cell Bioengineering, Ecole Polytechnique Fédérale de Lausanne, Lausanne, SwitzerlandIn 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.http://dx.doi.org/10.1063/5.0092860 |
| spellingShingle | 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 Microarrayed human bone marrow organoids for modeling blood stem cell dynamics APL Bioengineering |
| title | Microarrayed human bone marrow organoids for modeling blood stem cell dynamics |
| title_full | Microarrayed human bone marrow organoids for modeling blood stem cell dynamics |
| title_fullStr | Microarrayed human bone marrow organoids for modeling blood stem cell dynamics |
| title_full_unstemmed | Microarrayed human bone marrow organoids for modeling blood stem cell dynamics |
| title_short | Microarrayed human bone marrow organoids for modeling blood stem cell dynamics |
| title_sort | microarrayed human bone marrow organoids for modeling blood stem cell dynamics |
| url | http://dx.doi.org/10.1063/5.0092860 |
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