An Improved Protocol for Establishment of AML Patient-Derived Xenograft Models

Hassan, Nunki; Yang, Jonason; Wang, Jenny

doi:10.1016/j.xpro.2020.100156

Cited by 6 publications

(6 citation statements)

References 2 publications

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“…However, difficulty accessing patient biopsies remains a challenge. The successful engraftment reported in MSOD-B hOss was achieved using a lower amount of AML cells as compared to what is routinely used for generating AML PDXs ( 86 , 87 ), indicating that the hOss model may also be advantageous for studying patient materials of limited quantity. Together with the observed robust engraftment of patient material, this calls for the further evaluation of the MSOD-B hOss model as a personalized drug-testing platform.…”

Section: Discussionmentioning

confidence: 99%

Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis

et al. 2022

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The bone marrow microenvironment provides indispensable factors to sustain blood production throughout life. It is also a hotspot for the progression of hematologic disorders and the most frequent site of solid tumor metastasis. Preclinical research relies on xenograft mouse models, but these models preclude the human-specific functional interactions of stem cells with their bone marrow microenvironment. Instead, human mesenchymal cells can be exploited for the in vivo engineering of humanized niches, which confer robust engraftment of human healthy and malignant blood samples. However, mesenchymal cells are associated with major reproducibility issues in tissue formation. Here, we report the fast and standardized generation of human mini-bones by a custom-designed human mesenchymal cell line. These resulting humanized ossicles (hOss) consist of fully mature bone and bone marrow structures hosting a human mesenchymal niche with retained stem cell properties. As compared to mouse bones, we demonstrate superior engraftment of human cord blood hematopoietic cells and primary acute myeloid leukemia samples and also validate hOss as a metastatic site for breast cancer cells. We further report the engraftment of neuroblastoma patient-derived xenograft cells in a humanized model, recapitulating clinically described osteolytic lesions. Collectively, our human mini-bones constitute a powerful preclinical platform to model bone-developing tumors using patient-derived materials.

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Section: Discussionmentioning

confidence: 99%

Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis

et al. 2022

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“…7 , 8 Additionally, targeting of HAVCR2 or LAG-3 might help to minimize the slightly enhanced exhaustion observed in the CAR’TCR-T cell subpopulation of Triple-T. To this end, studying CAR’TCR-T cell functionality in a patient-derived xenograft mouse model would display a possible setting for testing such combinatorial strategies and to further verify our findings. 45 …”

Section: Discussionmentioning

confidence: 99%

CAR’TCR-T cells co-expressing CD33-CAR and dNPM1-TCR as superior dual-targeting approach for AML treatment

Teppert,

Yonezawa Ogusuku,

Brandes

et al. 2024

Molecular Therapy: Oncology

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“…Crossbreeding NOD/SCID and interleukin (IL)-2 receptor γ -deficient mice has produced triple immunodeficient NCG, NSG, or NOG mice that lack functional T , B , and NK cells and are available from a number of suppliers [ 26 ]. The use of the triple immunodeficient NSG and NOG mouse models has significantly improved the efficiency of ALL and AML tumor engraftment in mouse models [ 27 – 29 ]. Triple immunodeficient NCG mice are not yet widely used to generate PDX models.…”

Section: Discussionmentioning

confidence: 99%

Patient-derived intrafemoral orthotopic xenografts of peripheral blood or bone marrow from acute myeloid and acute lymphoblastic leukemia patients: clinical characterization, methodology, and validation

Chen

Zhao

et al. 2022

Clin Exp Med

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Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are malignant clonal diseases of the hematopoietic system with an unsatisfactory overall prognosis. The main obstacle is the increased resistance of AML and ALL cells to chemotherapy. The development and validation of new therapeutic strategies for acute leukemia require preclinical models that accurately recapitulate the genetic, pathological, and clinical features of acute leukemia. A patient-derived orthotopic xenograft (PDOX) model is established using surgical orthotopic implantation. They closely resemble human tumor progression and microenvironment and are more reliable translational research tools than subcutaneous-transplant models. In this study, we established PDOX models by direct intrafemoral injection of bone marrow and peripheral blood cells from AML and ALL patients, characterized their pathology, cytology, and genetics, and compared the model's characteristics and drug responsiveness with those of the corresponding patients.

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An Improved Protocol for Establishment of AML Patient-Derived Xenograft Models

Cited by 6 publications

References 2 publications

Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis

Engineering human mini-bones for the standardized modeling of healthy hematopoiesis, leukemia, and solid tumor metastasis

CAR’TCR-T cells co-expressing CD33-CAR and dNPM1-TCR as superior dual-targeting approach for AML treatment

Patient-derived intrafemoral orthotopic xenografts of peripheral blood or bone marrow from acute myeloid and acute lymphoblastic leukemia patients: clinical characterization, methodology, and validation

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