Evaluation of Epidermal Neural Crest Stem Cells in Organotypic Spinal Cord Slice Culture Platform.

Among various strategies employed for spinal cord injury, stem cell therapy is a potential treatment. So far, a variety of stem cells have been evaluated in animal models and humans with spinal cord injury, and epidermal neural crest stem cells represent one of the attractive types in this area. Although these multipotent stem cells have been assessed in several spinal cord injury models by independent laboratories, extensive work remains to be done to ascertain whether these cells can safely improve the outcome following human spinal cord injury. Among the models that closely mimic human spinal cord injury, the in vitro model of injury in organotypic spinal cord slice culture has been identified as one of the faithful platforms for injury-related investigations. In this study, green fluorescent protein-expressing stem cells were grafted into injured organotypic spinal cord slice culture and their survival was examined by confocal microscope seven days after transplantation. Data obtained from this preliminary study showed that these stem cells can survive on top of the surface of injured slices, as observed on day seven following their transplantation. This result revealed that this in vitro model of injury can be considered as a suitable context for further evaluation of epidermal neural crest stem cells before their application in large animals.

A novel rat model of Alzheimer's disease based on lentiviral-mediated expression of mutant APP.

BACKGROUND: Alzheimer's disease (AD) is characterized by progressive and irreversible cognitive and memory impairment. The discovery of familial forms of AD (fAD) in association with specific gene mutations facilitated the generation of numerous rodent models. These models in turn proved valuable for the study of molecular mechanisms underlying AD pathogenesis, and facilitated translational research and preclinical drug development. This study aimed to introduce a new rat model of AD simulating some aspects of the sporadic cases of disease. METHODS: Lentiviruses (LV) encoding human amyloid protein precursor (APP) bearing the fAD-linked Swedish and Indiana mutations (APPSw/Ind) were injected bilaterally in the hippocampus of adult rats. Passive avoidance and spatial memory performance were assessed 30 and 45 days post-injection, respectively. APP overexpression, intracellular accumulation of ß-amyloid (Aß) peptide, and astrogliosis were also evaluated using immunohistochemical procedures. RESULTS: Passive avoidance memory deficit was followed by impairments in spatial memory retrieval in LV (APPSw/Ind)-injected rats, compared to control animals. In addition, LV expression of APPSw/Ind was associated with intraneuronal accumulation of Aß, and reactive astrocytosis, two major AD hallmarks. CONCLUSION: Results from this work suggest that LV-mediated delivery of APPSw/Ind in adult rats represents a cost and time-effective animal model for the study of mechanisms underlying APP-linked fAD pathogenesis. The relevance of this animal model to the study of sporadic AD is discussed.