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Browsing by Author "Tate, Tiffany A."
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Item Bleeding the laboratory mouse: Not all methods are equal(Elsevier, 2016-02) Hoggatt, Jonathan; Hoggatt, Amber F.; Tate, Tiffany A.; Fortman, Jeffrey; Pelus, Louis M.; Microbiology and Immunology, School of MedicineThe laboratory mouse is the model most frequently used in hematologic studies and assessment of blood parameters across a broad range of disciplines. Often, analysis of blood occurs in a nonterminal manner. However, the small body size of the mouse limits collection based on volume, frequency, and accessible sites. Commonly used sites in the mouse include the retro-orbital sinus, facial vein, tail vein, saphenous vein, and heart. The method of blood acquisition varies considerably across laboratories and is often not reported in detail. In this study, we report significant alterations in blood parameters, particularly of total white blood cells, specific populations of dendritic cells and myeloid-derived suppressor cells, and hematopoietic progenitor cells, as a result of site and manner of sampling. Intriguingly, warming of mice prior to tail bleeding was found to significantly alter blood values. Our findings suggest that the same method should be used across an entire study, that mice should be warmed prior to tail bleeds to make levels uniform, and that accurate description of bleeding methods in publications should be provided to allow for interpretation of comparative reports and inter- and intralaboratory experimental variability.Item Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell(Elsevier, 2018-01-11) Hoggatt, Jonathan; Singh, Pratibha; Tate, Tiffany A.; Chou, Bin-Kuan; Datari, Shruti R.; Fukuda, Seiji; Liu, Liqiong; Kharchenko, Peter V.; Schajnovitz, Amir; Baryawno, Ninib; Mercier, Francois E.; Boyer, Joseph; Gardner, Jason; Morrow, Dwight M.; Scadden, David T.; Pelus, Louis M.; Microbiology and Immunology, School of MedicineHematopoietic stem cell transplantation is a potential curative therapy for malignant and nonmalignant diseases. Improving the efficiency of stem cell collection and the quality of the cells acquired can broaden the donor pool and improve patient outcomes. We developed a rapid stem cell mobilization regimen utilizing a unique CXCR2 agonist, GROβ, and the CXCR4 antagonist AMD3100. A single injection of both agents resulted in stem cell mobilization peaking within 15 min that was equivalent in magnitude to a standard multi-day regimen of granulocyte colony-stimulating factor (G-CSF). Mechanistic studies determined that rapid mobilization results from synergistic signaling on neutrophils, resulting in enhanced MMP-9 release, and unexpectedly revealed genetic polymorphisms in MMP-9 that alter activity. This mobilization regimen results in preferential trafficking of stem cells that demonstrate a higher engraftment efficiency than those mobilized by G-CSF. Our studies suggest a potential new strategy for the rapid collection of an improved hematopoietic graft.Item Role of lipegfilgrastim in the management of chemotherapy-induced neutropenia(Dovepress, 2015-04) Hoggatt, Jonathan; Tate, Tiffany A.; Pelus, Louis M.; Department of Microbiology and Immunology, IU School of MedicineChemotherapy, irradiation, and other agents are widely used to target the process of cell division in neoplastic cells. However, while these therapies are effective against most cancers, the high proliferative rate of the cells of the hematopoietic system that produce billions of blood cells needed daily throughout life is extremely sensitive to these agents, resulting in loss of blood cell populations, which can be life threatening. Neutropenia is the most serious hematologic toxicity of chemotherapy, which can result in patient morbidity and mortality due to opportunistic infection and often is the limiting factor in dose escalation or duration of chemotherapeutic administration. Neutropenic patients often require hospitalization and incur substantial medical costs associated with anti-infective therapy. Treatment of iatrogenic and congenic neutropenia was changed in the early 1990s with the introduction of filgrastim (Neupogen®) and pegfilgrastim (Neulasta®). With the expiration of patent lives of both of these drugs, biosimilars have begun to emerge. In this review, we will summarize the chemical characteristics, pharmacokinetics, safety and efficacy of lipegfilgrastim (Lonquex®), the first long-acting biosimilar filgrastim to receive regulatory approval and enter the marketplace.