Long-Term, Sex-Specific Effects of GCRsim and Gamma Irradiation on the Brains, Hearts, and Kidneys of Mice with Alzheimer's Disease Mutations.

Understanding the hazards of space radiation is imperative as astronauts begin voyaging on missions with increasing distances from Earth's protective shield. Previous studies investigating the acute or long-term effects of specific ions comprising space radiation have revealed threats to organs generally considered radioresistant, like the brain, and have shown males to be more vulnerable than their female counterparts. However, astronauts will be exposed to a combination of ions that may result in additive effects differing from those of any one particle species. To better understand this nuance, we irradiated 4-month-old male and female, wild-type and Alzheimer's-like mice with 0, 0.5, or 0.75 Gy galactic cosmic ray simulation (GCRsim) or 0, 0.75, or 2 Gy gamma radiation (wild-type only). At 11 months, mice underwent brain and heart MRIs or behavioral tests, after which they were euthanized to assess amyloid-beta pathology, heart and kidney gene expression and fibrosis, and plasma cytokines. Although there were no changes in amyloid-beta pathology, we observed many differences in brain MRIs and behavior, including opposite effects of GCRsim on motor coordination in male and female transgenic mice. Additionally, several genes demonstrated persistent changes in the heart and kidney. Overall, we found sex- and genotype-specific, long-term effects of GCRsim and gamma radiation on the brain, heart, and kidney.

Characterization of perfusion decellularized whole animal body, isolated organs, and multi-organ systems for tissue engineering applications.

To expand the application of perfusion decellularization beyond isolated single organs, we used the native vasculature of adult and neonatal rats to systemically decellularize the organs of a whole animal in situ. Acellular scaffolds were generated from kidney, liver, lower limb, heart-lung system, and a whole animal body, demonstrating that perfusion decellularization technology is applicable to any perfusable tissue, independent of age. Biochemical and histological analyses demonstrated that organs and organ systems (heart-lung pair and lower limb) were successfully decellularized, retaining their extracellular matrix (ECM) structure and organ-specific composition, as evidenced by differences in organ-specific scaffold stiffness. Altogether, we demonstrated that organs, organ systems and whole animal bodies can be perfusion decellularized while retaining ECM components and biomechanics.