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.

Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure

“…In addition to possessing hepatocyte-related functions, HLCs have been reported to exert inflammatory regulatory effects [ 37 ]. Therefore, we investigated the impact of HLCs supernatant on macrophage polarization.…”

“…Stem cell-derived HLCs are readily available with low immunogenicity. HLCs exhibit similar hepatic functions as primary hepatocytes and possess anti-inflammatory and regenerative effects [ [37] , [38] , [39] , 41 , 47 ]. Studies indicated that after hepatocyte differentiation, MSCs-derived HLCs gained hepatic functions including ALB formation, cytochrome P450 enzyme activity, urea secretion, and so on.…”

“…S21 revealed that HLCs prominently improved the ALB levels of ALF mice. Besides, HLCs possessed inherent anti-inflammatory activity [ [37] , [38] , [39] , 78 ], thereby synergistically protecting the host liver cells from oxidative stress and accelerating liver regeneration. Compared with the HLCs/Cu NZs@fiber/dECM group, the serological measurement showed that there was no significant increase in the ALB level of HLCs/fiber/dECM group ( Fig.…”

“…Studies have evidenced that MSCs can effectively differentiate into functional hepatocyte-like cells (HLCs) with customized cytokine cocktails [ 35 , 36 ]. MSC-derived HLCs not only retain anti-inflammatory activity, but also possess hepatic-specific functions [ [37] , [38] , [39] ]. Therefore, MSC-derived HLCs show great potential as the alternative cell source of hepatocyte therapy [ 31 , [40] , [41] , [42] ].…”

A retrospective observational study to assess the cirrhosis risk in alcoholic patients

“…Cirrhosis is a late-stage liver disease in which/ advanced stage of scaring and conditions, such as hepatitis and chronic alcoholism [1,2]. The liver carries out several necessary functions, including detoxifying harmful substances in your body, cleaning your blood, and making vital nutrients [3,4].…”