Liver failure secondary to hepatitis, hepatotoxin exposure, and cirrhosis threatens the lives of thousands in the United States alone. Estimates of yearly direct healthcare costs for liver disease in the U.S. range from $60 billion to over $100 billion. Vesta Therapeutics has developed proprietary technologies for the isolation and preservation of primary hepatocytes from livers that are not suitable for direct transplantation. They can isolate as many as 50 billion viable cells from a single liver that are suitable for infusion and transplantation in HLA matched recipients. A number of studies have demonstrated that adult stem cells isolated from multiple sites including adipose tissue have the potential to improve in vivo regeneration of damaged organs, including the liver and brain. Several mechanisms of organ recovery have been proposed. First, it is hypothesized that the transplanted adult stem cells directly differentiate in situ along the lineage pathway of the damaged tissue's primary functional cell type. Second, it is hypothesized that the transplanted adult stem cells fuse directly to the recipient's primary cells at the site of injury and reinvigorate their function. Finally, it is hypothesized that the transplanted adult stem cells release cytokines and growth factors at the site of injury in the recipient; these, in turn, promote the recovery of the recipient's endogenous functional cells. Independent of the mechanism of adult stem cell action, these studies suggest that adult stem cell transplantation offers a treatment modality that safely and effectively improves biochemical function within the failing liver. Vesta Therapeutics, in collaboration with Dr. Gimble (Pennington Biomedical Research Center), will explore the use of adipose derived adult stem (ADAS) cells as a therapeutic modality in liver disease through the following Specific Aims: (1) To demonstrate the ability of human and murine ADAS cells to express biochemical differentiation markers of hepatocytes or hepatic parenchymal cells in vitro; (2) To demonstrate the ability of human and murine ADAS cells to express hepatic growth factor (HGF) and cytokines associated with liver regeneration. The results of these studies may lead to novel mechanisms to treat and manage patients with liver failure and have potential significant clinical and economic benefit. We will pursue promising in vitro Phase I outcomes with in vivo Phase II proof of concept experiments
