Conclusion: Transplantation studies indicate that the state of the host microenvironment is critical to the regenerative potential of hepatocytes, and that a change in the extracellular matrix can lead to regeneration and restoration of function by cells derived from livers with end-stage organ failure. (HEPATOLOGY 2011) Expansion and altered composition of the extracellular matrix as a result of collagen deposition is a common response to injury and plays a major role in chronic heart, liver, and kidney

failure. Understanding the extent to which reversal of this process can lead to functional organ recovery is a critical issue, as numerous interventions have been proposed to improve fibrosis and presumably reverse organ failure.1-4 The unique capacity of hepatic parenchymal cells to undergo extensive proliferation in response to injury makes the liver check details an ideal organ to study cellular regeneration in acquired chronic disease. In the liver, expansion of the extracellular matrix with capillarization of the sinusoidal endothelium and loss of fenestrae results in cirrhosis with production selleck chemicals of regenerative hepatic nodules, portal hypertension, loss of hepatocytes, and liver failure.5 Loss of significant hepatocyte mass does not routinely produce hepatic failure, because the liver is capable

of normal function with less than half its normal complement of hepatocytes.6, 7 Thus, the cause of organ failure in cirrhosis is not well understood. Impaired hepatic function results from intrinsic damage to the native liver cells and from the abnormal

microenvironment in which they reside.8-14 Because collagen deposition and vascular changes in cirrhosis can be extensive before there is functional hepatic decompensation, it is not clear to what extent each plays a role or at what point these factors tip parenchymal cell function toward organ failure. Mito et al.15 attempted to address the role of the microenvironment in hepatic failure by transplanting medchemexpress hepatocytes from the livers of patients with cirrhosis back into their own spleens to reverse decompensated liver disease. If it is possible to recover the function of parenchymal cells from a cirrhotic liver by changing the microenvironment, it may be possible to restore hepatic function in the cirrhotic liver by reversing hepatic structural abnormalities, and individual cells derived from some cirrhotic livers might prove to be useful as an untapped source of transplantable cells for the treatment of patients with liver-based metabolic disorders, where the liver microenvironment is intact. Here, we demonstrate that primary cells derived from cirrhotic livers with decompensated function exhibit severe alterations in gene expression and defects in proliferative capacity and function directly after isolation, but engraft normally in a noncirrhotic microenvironment.