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Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm3 to 62 mm3, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.
One of the identified health risk areas for human spaceflight is infectious disease, particularly involving environmental microorganisms already found on the International Space Station (ISS). In particular, bacteria belonging to the Burkholderia cepacia complex (Bcc) which can cause human disease in those who are immunocompromised, have been identified in the ISS water supply. This present study characterized the effect of spaceflight analog culture conditions on Bcc to certain physiological stresses (acid and thermal as well as intracellular survival in U927 human macrophage cells). The NASA-designed Rotating Wall Vessel (RWV) bioreactor was used as the spaceflight analogue culture system in these studies to grow Bcc bacterial cells under Low Shear Modeled Microgravity (LSMMG) conditions. Results show that LSMMG culture increased the resistance of Bcc to both acid and thermal stressors, but did not alter phagocytic uptake in 2-D monolayers of human monocytes.
Collectively, this work represents the first characterization of in vivo virulence and in vitro pathogenesis properties of D23580, the latter using advanced human surrogate models that mimic key aspects of the parental tissue. Results from these studies highlight the importance of studying infectious diseases using an integrated approach that combines actions of biological and physical networks that mimic the host-pathogen microenvironment and regulate pathogen responses.