Browsing by Subject "Mobilization"

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2
    (Springer Nature, 2013) Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Chitteti, Brahmananda Reddy; Speth, Jennifer M.; Hu, Peirong; Poteat, Bradley A.; Stilger, Kayla N.; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Farag, Sherif S.; Czader, Magdalena; Milne, Ginger L.; Breyer, Richard M.; Serezani, Carlos H.; Scadden, David T.; Guise, Theresa; Srour, Edward F.; Pelus, Louis M.; Medicine, School of Medicine
    To maintain lifelong production of blood cells, haematopoietic stem cells (HSCs) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSCs reside in several, perhaps overlapping, niches that produce regulatory molecules and signals necessary for homeostasis and for increased output after stress or injury. Despite considerable advances in the specific cellular or molecular mechanisms governing HSC-niche interactions, little is known about the regulatory function in the intact mammalian haematopoietic niche. Recently, we and others described a positive regulatory role for prostaglandin E2 (PGE2) on HSC function ex vivo. Here we show that inhibition of endogenous PGE2 by non-steroidal anti-inflammatory drug (NSAID) treatment in mice results in modest HSC egress from the bone marrow. Surprisingly, this was independent of the SDF-1-CXCR4 axis implicated in stem-cell migration. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin. Haematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in other species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced E-prostanoid 4 (EP4) receptor signalling. These results not only uncover unique regulatory roles for EP4 signalling in HSC retention in the niche, but also define a rapidly translatable strategy to enhance transplantation therapeutically.
  • Thumbnail Image
    Item
    Increased mobilization and yield of stem cells using plerixafor in combination with granulocyte-colony stimulating factor for the treatment of non-Hodgkin’s lymphoma and multiple myeloma
    (Dove Press, 2011-02-27) Pelus, Louis M.; Farag, Sherif S.; Microbiology and Immunology, School of Medicine
    Multiple myeloma and non-Hodgkin's lymphoma remain the most common indications for high-dose chemotherapy and autologous peripheral blood stem cell rescue. While a CD34+ cell dose of 1 × 10(6)/kg is considered the minimum required for engraftment, higher CD34+ doses correlate with improved outcome. Numerous studies, however, support targeting a minimum CD34+ cell dose of 2.0 × 10(6)/kg, and an "optimal" dose of 4 to 6 × 10(6)/kg for a single transplant. Unfortunately, up to 40% of patients fail to mobilize an optimal CD34+ cell dose using myeloid growth factors alone. Plerixafor is a novel reversible inhibitor of CXCR4 that significantly increases the mobilization and collection of higher numbers of hematopoietic progenitor cells. Two randomized multi-center clinical trials in patients with non-Hodgkin's lymphoma and multiple myeloma have demonstrated that the addition of plerixafor to granulocyte-colony stimulating factor increases the mobilization and yield of CD34+ cells in fewer apheresis days, which results in durable engraftment. This review summarizes the pharmacology and evidence for the clinical efficacy of plerixafor in mobilizing hematopoietic stem and progenitor cells, and discusses potential ways to utilize plerixafor in a cost-effective manner in patients with these diseases.
  • Thumbnail Image
    Item
    Sowing the Seeds of a Fruitful Harvest: Hematopoietic Stem Cell Mobilization
    (Wiley, 2013-12) Hoggatt, Jonathan; Speth, Jennifer M.; Pelus, Louis M.; Department of Microbiology & Immunology, School of Medicine
    Hematopoietic stem cell transplantation is the only curative option for a number of malignant and non-malignant diseases. As the use of hematopoietic transplant has expanded, so too has the source of stem and progenitor cells. The predominate source of stem and progenitors today, particularly in settings of autologous transplantation, is mobilized peripheral blood. This review will highlight the historical advances which lead to the widespread use of peripheral blood stem cells for transplantation, with a look towards future enhancements to mobilization strategies.
  • Thumbnail Image
    Item
    The War in the Classroom: The Work of the Educational Section of the Indiana State Council of Defense during World War I
    (2012) Schuster, Casey Elizabeth; Barrows, Robert G. (Robert Graham), 1946-; Robertson, Nancy Marie, 1956-; Cramer, Kevin
    When the United States entered World War I in April 1917, many Americans quickly rallied to support the nation. Among the numerous committees, organizations, and individuals that became active in the mobilization process were the forty-eight state councils of defense. Encouraged to form by President Wilson and his administration in the days and weeks following U.S entry in the war, the state councils grew as offshoots of the Council of National Defense and assisted in bringing every section of the country into a single scheme of work. Everyone was expected to do their part in WWI, whether they were fighting overseas or helping on the home front. The state councils, broken down into various sections and county, township, and high-school level councils, made sure that this was the case by reaching down into local communities and encouraging individuals to become involved in the war effort. Their work represented the embodiment of a “total war” philosophy and, yet, studies on these organizations are surprisingly scarce, giving readers an inadequate understanding of the American home front during the conflict. This thesis therefore places the focus directly on the state councils and examines the work they undertook to make the United States ready for, and most effective in wartime service. In particular, it explores the efforts of the Educational Section of the Indiana State Council of Defense. By concentrating on this one section, readers may gain a better understanding of the lengths that the state councils went to in order to put every person – teachers and students included – on a wartime footing.