Browsing by Subject "Hematopoietic cell transplant"

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    Impacts of SDF-1 and radiation dose-rate in an adult zebrafish model of hematopoietic cell transplant
    (2013-05) Glass, Tiffany
    Despite a history of refinements, Hematopoietic Cell Transplant (HCT) remains a potentially difficult treatment that can have high risks for complications and mortality. We used adult zebrafish models of HCT to study two broad biological processes that occur during HCT; homing and early donor-derived hematopoietic reconstitution. In the first case, we validated the adult zebrafish model for the study of the chemokine SDF-1 in HCT, developed a transgenic sdf-1 reporter zebrafish line, and used it to determine sites of high sdf-1 expression in recipient organisms. These sites were discovered both in the hematopoietic tissue as well as in previously un-described structures throughout the skin, and were found to consistently attract donor-derived cells after transplant. Ultimately, this allowed the identification of new putative HSC-niche cells which can be isolated with relative ease. Secondly, we assessed the effects of high conditioning radiation dose-rates on the process of hematopoietic engraftment after transplant. In groups of adult zebrafish given the same total dose of preconditioning radiation, we found that recipients irradiated at a high rate show significantly faster engraftment compared to those irradiated at a lower rate. Insights offered by this work will contribute to future efforts identifying endogenous factors promoting rapid engraftment, as well as to future reassessments of therapeutic opportunities offered by biologically informed refinements of preconditioning radiation strategies.
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    In vivo assessment of hematopoietic cell homing and engraftment in zebrafish using bioluminescence imaging
    (2013-05) Astuti, Yuliana Sakti Dwi
    Hematopoietic cell transplantation (HCT) has been increasingly used as treatment for malignant and non-malignant diseases over the past 40 years. Despite many advancements made in the field, this procedure continues to face some major challenges, including graft versus host disease and the limited donor availability. Current researches are directed at expanding the number of hematopoietic stem cells and/or improving the HSC homing, especially when the donor cell number is low. Zebrafish has emerged as a versatile organism to study HCT due to its cost-effectiveness and high degree of genetic similarities to mammals. As post-mortem analysis of engraftment following HCT does not offer rapid and long-term continuous monitoring of the engraftment process, we sought to use bioluminescence imaging (BLI) in our HCT study. We generated transgenic zebrafish line that ubiquitously expressed the firefly luciferase. We optimized the anesthesia regiments and the BLI settings used in our system. Finally, using in vivo BLI, we were able to longitudinally monitor the dynamic of donor cells in the transplant recipients and observe the effect of ex vivo prostaglandin E2 treatment on the early donor cell engraftment and the survival of the transplant recipients.