Modeling Chronic Graft Versus Host Disease in Mice Using Allogeneic Bone Marrow and Splenocyte Transfer

Schroeder, Mark A.; Ashami, Kidist; Staser, Karl

doi:10.1002/cpph.47

Cited by 5 publications

(6 citation statements)

References 17 publications

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“…To assess the IQAD biosensor in the context of GVHD, bone marrow cells and splenocytes were isolated from IQAD biosensor mice and transferred into irradiated WT C57BL/6 mice (syngeneic transfer) or BALB/c mice (allogeneic transfer). As a control, bone marrow cells only were transferred into irradiated allogeneic recipients, as this is necessary to reconstitute the host hematopoietic system but does not cause GVHD in mice (65)(66)(67). At various time points posttransfer, mice were imaged in vivo and bioluminescence was quantified.…”

Section: Iqad Biosensors Are Activated In Alloreactive Donor Cells Dumentioning

confidence: 99%

A Caspase-1 Biosensor to Monitor the Progression of Inflammation In Vivo

Talley

Kalinina

Winek

et al. 2019

The Journal of Immunology

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Inflammasomes are multiprotein complexes that coordinate cellular inflammatory responses and mediate host defense. Following recognition of pathogens and danger signals, inflammasomes assemble and recruit and activate caspase-1, the cysteine protease that cleaves numerous downstream targets, including pro–IL-1β and pro–IL-18 into their biologically active form. In this study, we sought to develop a biosensor that would allow us to monitor the initiation, progression, and resolution of inflammation in living animals. To this end, we inserted a known caspase-1 target sequence into a circularly permuted luciferase construct that becomes bioluminescent upon protease cleavage. This biosensor was activated in response to various inflammatory stimuli in human monocytic cell lines and murine bone marrow–derived macrophages. Next, we generated C57BL/6 transgenic mice constitutively expressing the caspase-1 biosensor. We were able to monitor the spatiotemporal dynamics of caspase-1 activation and onset of inflammation in individual animals in the context of a systemic bacterial infection, colitis, and acute graft-versus-host disease. These data established a model whereby the development and progression of inflammatory responses can be monitored in the context of these and other mouse models of disease.

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Section: Iqad Biosensors Are Activated In Alloreactive Donor Cells Dumentioning

confidence: 99%

A Caspase-1 Biosensor to Monitor the Progression of Inflammation In Vivo

Talley

Kalinina

Winek

et al. 2019

The Journal of Immunology

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“…Two of the three mice that survived for 45 days were still alive 100 days after transplant. GvHD progression was assessed using an established scoring system [ 21 , 22 ]. Mice were monitored daily, or every other day, and changes of weight, posture, activity, fur texture, and skin integrity were recorded and scored.…”

Section: Resultsmentioning

confidence: 99%

“…The model was determined according to several considerations. First, preliminary data showed reduced transduction efficacy of MSC from BALB/c mice, characterized by lower levels of coxsackievirus and adenovirus receptor (CAR) expression [ 22 ]. Second, the conditions of MSC transduction were experimentally tested, taking into account several considerations.…”

Section: Discussionmentioning

confidence: 99%

“…We chose to use for our model an infusion of 3 × 10 7 splenocytes, a dose for which all untreated mice die within 30 days from transplantation. Monitoring of the mice was performed daily, or every other day, using an established aGvHD clinical grading system initially proposed by Cooke et al [ 21 ] and modified by Schroeder et al [ 22 ]. Weight loss, hunched posture, skin integrity, fur aspect, and activity were each assigned scores of 0 (absent), 1 (moderate), or 2 (severe).…”

Section: Methodsmentioning

confidence: 99%

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Treatment with Mesenchymal Stromal Cells Overexpressing Fas-Ligand Ameliorates Acute Graft-versus-Host Disease in Mice

Vacaru¹,

Mazilu²,

Dumitrescu³

et al. 2022

IJMS

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Allogeneic hematopoietic cell transplantation (allo-HCT) has the potential to cure malignant and non-malignant hematological disorders, but because of the serious side effects of this intervention its applications are limited to a restricted number of diseases. Graft-versus-host disease (GvHD) is the most frequent complication and the leading cause of mortality and morbidity following allo-HCT. It results from the attack of the transplanted T cells from the graft against the cells of the recipient. There is no clear treatment for this severe complication. Due to their immunomodulatory properties, mesenchymal stromal cells (MSC) have been proposed to treat GvHD, but the results did not meet expectations. We have previously showed that the immunomodulatory effect of the MSC was significantly enhanced through adenoviral-mediated overexpression of FasL. In this study, we have tested the properties of FasL-overexpressing MSC in vivo, in a mouse model for acute GvHD. We found that treatment with FasL-overexpressing MSC delayed the onset of the disease and increased survival of the mice.

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“…Human PBMCs in NSG mice can cause graft-versus-host disease (GvHD) within 6 weeks of hPBMC engraftment [ 31 ]. We did not observe signs of GvHD histopathologically or grossly in the time we used our model, except for two mice that had hair loss and decreased overall survival, a possible sign of skin GvHD [ 32 ]. An alternative strategy to humanize mice with immune cells would be to perform bone marrow transplantation with CD34 + human hematopoietic stem cells.…”

Section: Discussionmentioning

confidence: 99%

A murine model to evaluate immunotherapy effectiveness for human Fanconi anemia-mutated acute myeloid leukemia

Huang,

Leung,

Huang

et al. 2024

PLoS ONE

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Fanconi anemia (FA)-mutated acute myeloid leukemia (AML) is a secondary AML with very poor prognosis and limited therapeutic options due to increased sensitivity to DNA-damaging agents. PD-1 immune checkpoint inhibitors upregulate T-cell killing of cancer cells and is a class of promising treatment for FA-AML. Here, we developed a novel FA-AML murine model that allows the study of human AML with a humanized immune system in order to investigate immunotherapeutic treatments in vivo. FA-AML1 cells and non-FA-mutated Kasumi-1 cells were injected into 8–10 week old NSG mice. Once leukemic engraftment was confirmed by HLA-DR expression in the peripheral blood, human peripheral blood mononuclear cells (hPBMCs) were injected into the mice. One week post-hPBMCs injection, Nivolumab (PD-1 inhibitor) or PBS vehicle control was administered to the mice bi-weekly. In our Nivolumab treated mice, FA-AML1, but not Kasumi-1-engrafted mice, had significantly prolonged overall survival. Both FA-AML1 and Kasumi-1 engrafted mice had decreased spleen weights. Higher leukemic infiltration into vital organs was observed in FA-AML1 engrafted mice compared to Kasumi-1 engrafted mice. In conclusion, our novel humanized murine model of FA-mutated AML is an attractive tool for supporting further studies and clinical trials using PD-1 inhibitors to treat FA-mutated AML.

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Modeling Chronic Graft Versus Host Disease in Mice Using Allogeneic Bone Marrow and Splenocyte Transfer

Cited by 5 publications

References 17 publications

A Caspase-1 Biosensor to Monitor the Progression of Inflammation In Vivo

A Caspase-1 Biosensor to Monitor the Progression of Inflammation In Vivo

Treatment with Mesenchymal Stromal Cells Overexpressing Fas-Ligand Ameliorates Acute Graft-versus-Host Disease in Mice

A murine model to evaluate immunotherapy effectiveness for human Fanconi anemia-mutated acute myeloid leukemia

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