Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation

Patient‐derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps...

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Main Authors: Daniel Busa, Zdenka Herudkova, Jan Hyl, Jakub Vlazny, Filip Sokol, Kvetoslava Matulova, Adam Folta, Jakub Hynst, Lucy Vojtova, Leos Kren, Martin Repko, Zdenek Racil, Jiri Mayer, Martin Culen
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Molecular Oncology
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Online Access:https://doi.org/10.1002/1878-0261.13790
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author Daniel Busa
Zdenka Herudkova
Jan Hyl
Jakub Vlazny
Filip Sokol
Kvetoslava Matulova
Adam Folta
Jakub Hynst
Lucy Vojtova
Leos Kren
Martin Repko
Zdenek Racil
Jiri Mayer
Martin Culen
author_facet Daniel Busa
Zdenka Herudkova
Jan Hyl
Jakub Vlazny
Filip Sokol
Kvetoslava Matulova
Adam Folta
Jakub Hynst
Lucy Vojtova
Leos Kren
Martin Repko
Zdenek Racil
Jiri Mayer
Martin Culen
author_sort Daniel Busa
collection DOAJ
description Patient‐derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps required to create the humanized scaffolds and achieve successful acute myeloid leukemia (AML) engraftment. We compared seven biomaterials, which included both published and custom‐designed materials. The highest level of bone marrow niche was achieved with extracellular matrix gels and custom collagen fiber, both of which allowed for a simple non‐surgical implantation. The biomaterial selection did not influence the following AML infiltration. Regarding xenotransplantation, standard intravenous administration produced the most robust engraftment, even for two out of four otherwise non‐engrafting AML samples. In contrast, direct intra‐scaffold xenotransplantation did not offer any advantage. In summary, we demonstrate that the combination of an injectable biomaterial for scaffold creation plus an intravenous route for AML xenotransplantation provide the most convenient and robust approach to produce AML PDX using a humanized niche.
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spelling doaj-art-73e6987ef8df443bb7709d49690cb6052025-08-20T01:50:39ZengWileyMolecular Oncology1574-78911878-02612025-05-011951371138510.1002/1878-0261.13790Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantationDaniel Busa0Zdenka Herudkova1Jan Hyl2Jakub Vlazny3Filip Sokol4Kvetoslava Matulova5Adam Folta6Jakub Hynst7Lucy Vojtova8Leos Kren9Martin Repko10Zdenek Racil11Jiri Mayer12Martin Culen13Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University Brno Czech RepublicDepartment of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University Brno Czech RepublicDepartment of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University Brno Czech RepublicDepartment of Pathology University Hospital Brno Czech RepublicDepartment of Pathology University Hospital Brno Czech RepublicDepartment of Pathology University Hospital Brno Czech RepublicDepartment of Internal Medicine, Hematology and Oncology University Hospital Brno Czech RepublicCentral European Institute of Technology Masaryk University Brno Czech RepublicCentral European Institute of Technology Brno Institute of Technology Czech RepublicDepartment of Pathology University Hospital Brno Czech RepublicOrthopedic Clinic University Hospital Brno Czech RepublicDepartment of Physiology, Faculty of Medicine Masaryk University Brno Czech RepublicDepartment of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University Brno Czech RepublicDepartment of Internal Medicine, Hematology and Oncology, Faculty of Medicine Masaryk University Brno Czech RepublicPatient‐derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps required to create the humanized scaffolds and achieve successful acute myeloid leukemia (AML) engraftment. We compared seven biomaterials, which included both published and custom‐designed materials. The highest level of bone marrow niche was achieved with extracellular matrix gels and custom collagen fiber, both of which allowed for a simple non‐surgical implantation. The biomaterial selection did not influence the following AML infiltration. Regarding xenotransplantation, standard intravenous administration produced the most robust engraftment, even for two out of four otherwise non‐engrafting AML samples. In contrast, direct intra‐scaffold xenotransplantation did not offer any advantage. In summary, we demonstrate that the combination of an injectable biomaterial for scaffold creation plus an intravenous route for AML xenotransplantation provide the most convenient and robust approach to produce AML PDX using a humanized niche.https://doi.org/10.1002/1878-0261.13790AMLcollagenmouse modelossiclespatient‐derived xenograftsT‐cell
spellingShingle Daniel Busa
Zdenka Herudkova
Jan Hyl
Jakub Vlazny
Filip Sokol
Kvetoslava Matulova
Adam Folta
Jakub Hynst
Lucy Vojtova
Leos Kren
Martin Repko
Zdenek Racil
Jiri Mayer
Martin Culen
Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation
Molecular Oncology
AML
collagen
mouse model
ossicles
patient‐derived xenografts
T‐cell
title Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation
title_full Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation
title_fullStr Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation
title_full_unstemmed Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation
title_short Robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation
title_sort robust acute myeloid leukemia engraftment in humanized scaffolds using injectable biomaterials and intravenous xenotransplantation
topic AML
collagen
mouse model
ossicles
patient‐derived xenografts
T‐cell
url https://doi.org/10.1002/1878-0261.13790
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