Clinical Application of Induced Hepatocyte-like Cells Produced from Mesenchymal Stromal Cells: A Literature Review

Abstract

Liver disease is a leading cause of mortality worldwide, resulting in 1.3 million deaths annually. The vast majority of liver disease is caused by metabolic disease (i.e., NASH) and alcohol-induced hepatitis, and to a lesser extent by acute and chronic viral infection. Furthermore, multiple insults to the liver is becoming common due to the prevalence of metabolic and alcohol-related liver diseases. Despite this rising prevalence of liver disease, there are few treatment options: there are treatments for viral hepatitis C and there is vaccination for hepatitis B. Aside from the management of metabolic syndrome, no direct liver therapy has shown clinical efficacy for metabolic liver disease, there is very little for acute alcohol-induced liver disease, and liver transplantation remains the only effective treatment for late-stage liver disease. Traditional pharmacologic interventions have failed to appreciably impact the pathophysiology of alcohol-related liver disease or end-stage liver disease. The difficulties associated with developing liver-specific therapies result from three factors that are common to late-stage liver disease arising from any cause: hepatocyte injury, inflammation, and aberrant tissue healing. Hepatocyte injury results in tissue damage with inflammation, which sensitizes the liver to additional hepatocyte injury and stimulates hepatic stellate cells and aberrant tissue healing responses. In the setting of chronic liver insults, there is progressive scarring, the loss of hepatocyte function, and hemodynamic dysregulation. Regenerative strategies using hepatocyte-like cells that are manufactured from mesenchymal stromal cells may be able to correct this pathophysiology through multiple mechanisms of action. Preclinical studies support their effectiveness and recent clinical studies suggest that cell replacement therapy can be safe and effective in patients with liver disease for whom there is no other option.