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Long-term engraftment of engineered human plasma cells

ABSTRACT: Long-term engraftment of engineered human plasma cells

PROVIDER: PRJNA873089 | ENA |

REPOSITORIES: ENA

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Long-term engraftment of engineered human plasma cells

Project description:Due to their unique longevity and capacity to secrete high levels of protein, plasma B cells play have the potential to be used as a cell therapy for protein replacement. Here, we show that ex vivo engineered human plasma cells exhibited transcriptional features of long-lived plasma cells.

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Stromal Repair via Long-term Engraftment of Primary Bone Marrow Stroma Improves Hematopoietic Stem Cell Transplantation

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Human IL-6 fosters long-term engraftment of human patient derived myeloma cells in immunodeficient mice

Project description:Multiple myeloma is a largely incurable and life-threatening malignancy of antibody-secreting plasma cells. An effective and widely available animal model that recapitulates human myeloma and related plasma cell disorders is lacking. We show that busulfan-conditioned hIL-6 transgenic NSG mice (NSG+hIL6) reliably support the engraftment of malignant and pre-malignant human plasma cells including from patients diagnosed with pre- and post-relapse myeloma, plasma cell leukemia, and AL amyloidosis. Consistent with human disease, NSG+hIL6 mice engrafted with patient-derived myeloma cells developed blood M spikes, and a majority developed anemia, hypercalcemia, and/or bone lesions. Singe cell RNAseq analyses showed non-malignant and malignant cell engraftment, the latter expressing a wide array of mRNAs associated with myeloma cell survival and proliferation. Myeloma-engrafted mice given CAR T-cells targeting plasma cells or bortezomib experienced reduced tumor burden. Our results establish that NSG+hIL6 mice provide an effective patient derived xenograft model for study and preclinincal drug development for myeloma and related plasma cell disorders.

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Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity

Project description:Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity

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High-throughput characterization of hematopoietic stem cell engraftment after intravenous and intracerebroventricular dosing

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Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [II]

Project description:Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [II]

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Human IL-6 fosters long-term engraftment of human patient derived myeloma cells in immunodeficient mice

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Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [I]

Project description:Infection drives long-term meningeal engraftment by inflammatory monocytes that impair central nervous system immunity [I]

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Project description:HMGA2 Promotes Long-Term Engraftment and Myelo-Erythroid Differentiation of Human Hematopoietic Stem and Progenitor Cells