Derivation of induced pluripotent stem cells from ferret somatic cells.

Ferrets are an attractive mammalian model for several diseases, especially those affecting the lungs, liver, brain, and kidneys. Many chronic human diseases have been difficult to model in rodents due to differences in size and cellular anatomy. This is particularly the case for the lung, where ferrets provide an attractive mammalian model of both acute and chronic lung diseases, such as influenza, cystic fibrosis, A1A emphysema, and obliterative bronchiolitis, closely recapitulating disease pathogenesis, as it occurs in humans. As such, ferrets have the potential to be a valuable preclinical model for the evaluation of cell-based therapies for lung regeneration and, likely, for other tissues. Induced pluripotent stem cells (iPSCs) provide a great option for provision of enough autologous cells to make patient-specific cell therapies a reality. Unfortunately, they have not been successfully created from ferrets. In this study, we demonstrate the generation of ferret iPSCs that reflect the primed pluripotent state of human iPSCs. Ferret fetal fibroblasts were reprogrammed and acquired core features of pluripotency, having the capacity for self-renewal, multilineage differentiation, and a high-level expression of the core pluripotency genes and pathways at both the transcriptional and protein level. In conclusion, we have generated ferret pluripotent stem cells that provide an opportunity for advancing our capacity to evaluate autologous cell engraftment in ferrets.

Sex-specific effects of high fat diet on indices of metabolic syndrome in 3xTg-AD mice: implications for Alzheimer's disease.

Multiple factors of metabolic syndrome have been implicated in the pathogenesis of Alzheimer's disease (AD), including abdominal obesity, insulin resistance, endocrine dysfunction and dyslipidemia. High fat diet, a common experimental model of obesity and metabolic syndrome, has been shown to accelerate cognitive decline and AD-related neuropathology in animal models. However, sex interacts with the metabolic outcomes of high fat diet and, therefore, may alter neuropathological consequences of dietary manipulations. This study examines the effects of sex and high fat diet on metabolic and AD-related neuropathological outcomes in 3xTg-AD mice. Three month-old male and female 3xTg-AD mice were fed either standard or high fat diets for 4 months. Obesity was observed in all high fat fed mice; however, ectopic fat accumulation, hyperglycemia and hyperinsulinemia were observed only in males. Interestingly, despite the different metabolic outcomes of high fat diet, the neuropathological consequences were similar: both male and female mice maintained under high fat diet exhibited significant worsening in behavioral performance and hippocampal accumulation of ß-amyloid protein. Because high fat diet resulted in obesity and increased AD-like pathology in both sexes, these data support a role of obesity-related factors in promoting AD pathogenesis.