Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis.

Skin sensitization remains a major environmental and occupational health hazard. Animal models have been used as the gold standard method of choice for estimating chemical sensitization potential. However, a growing international drive and consensus for minimizing animal usage have prompted the development of methods to assess chemical sensitivity.

Development of Metabolic Indicators of Burn Injury: Very Low Density Lipoprotein (VLDL) and Acetoacetate Are Highly Correlated to Severity of Burn Injury in Rats.

Hypermetabolism is a significant sequela to severe trauma such as burns, as well as critical illnesses such as cancer. It persists in parallel to, or beyond, the original pathology for many months as an often-fatal comorbidity. Currently, diagnosis is based solely on clinical observations of increased energy expenditure, severe muscle wasting and progressive organ dysfunction.

Metabolic profiling based quantitative evaluation of hepatocellular metabolism in presence of adipocyte derived extracellular matrix.

The elucidation of the effect of extracellular matrices on hepatocellular metabolism is critical to understand the mechanism of functional upregulation. We have developed a system using natural extracellular matrices [Adipogel] for enhanced albumin synthesis of rat hepatocyte cultures for a period of 10 days as compared to collagen sandwich cultures. Primary rat hepatocytes isolated from livers of female Lewis rats recover within 4 days of culture from isolation induced injury while function is stabilized at 7 days post-isolation.

In situ metabolic flux analysis to quantify the liver metabolic response to experimental burn injury.

Trauma such as burns induces a hypermetabolic response associated with altered central carbon and nitrogen metabolism. The liver plays a key role in these metabolic changes; however, studies to date have evaluated the metabolic state of liver using ex vivo perfusions or isotope labeling techniques targeted to specific pathways. Herein, we developed a unique mass balance approach to characterize the metabolic state of the liver in situ, and used it to quantify the metabolic changes to experimental burn injury in rats.

Adipocyte-derived basement membrane extract with biological activity: applications in hepatocyte functional augmentation in vitro.

Natural and synthetic biomaterials utilized in tissue engineering applications require a dynamic interplay of complex macromolecular compositions of hydrated extracellular matrices (ECMs) and soluble growth factors. The challenges in utilizing synthetic ECMs is the effective control of temporal and spatial complexity of multiple signal presentation, as compared to natural ECMs that possess the inherent properties of biological recognition, including presentation of receptor-binding ligands, susceptibility to cell-triggered proteolytic degradation, and remodeling. We have developed a murine preadipocyte differentiation system for generating a natural basement membrane extract (Adipogel) comprising ECM proteins (collagen IV, laminin, hyaluronan, and fibronectin) and including relevant growth factors (hepatocyte growth factor, vascular endothelial growth factor, and leukemia inhibitory factor).

Enrichment of hepatocyte-like cells with upregulated metabolic and differentiated function derived from embryonic stem cells using S-NitrosoAcetylPenicillamine.

The generation of a large number of fully functional hepatocytes from a renewable cell source can provide an unlimited resource for bioartificial liver devices and cell replacement therapies. We have established a directed differentiation system using sodium butyrate treatment to generate an enriched population of hepatocyte-like cells from embryonic stem cells. A metabolic analysis of the hepatocyte populations revealed glycolytic and mitochondrial phenotypes similar to mouse hepatoma cells, implying that these cells represent an immature hepatocyte phenotype.