Mesenchymal Stem Cell Therapy for Liver Cirrhosis Treatment: Mechanisms and Bioeffects

Nhung Hai Truong and Phuc Van Pham

Introduction

The liver plays a vital role as a metabolism machinery with the following main functions: absorption of nutrients, elimination of toxins, energy storage, control of blood sugar, and production of protein (e.g., bile and blood clotting factors, transport proteins, etc.). The liver is the only organ in the body that can easily regenerate damaged cells. Notably, the liver shows limited cell turnover, but as soon as cell damage occurs, the regenerative process is enhanced rapidly to recover and maintain organ function (Alison et al. 2009). Although the liver compensatory regeneration is a rapid and efficient process, sometimes liver cells may not able to be restored, as in the case with massive hepatocyte damage, in which case liver failure occurs. Though there are many causes of chronic liver disease, the consequences are the same. Liver injury may cause liver cirrhosis that leads to reduction of liver function and induction hepatocellular carcinoma (HCC) (Forbes 2009; Stefan et al. 2015).

Cirrhosis is defined as the replacement of healthy liver tissues by fibrosis and regenerative nodule formation. Cirrhosis ranks 14th in the world and 4th in Central Europe as cause of death (Tsochatzis et al. 2014). Currently, cirrhosis is listed among the 25 diseases with the highest mortality worldwide. There are many different causes leading to liver cirrhosis; these include viral hepatitis, alcohol, cholestatic phenomenon, and toxic chemicals. In particular, hepatitis B virus (HBV)-associated disease causes the highest mortality rate, up to 4.8/100,000 people (Moon et al. 2009; Murray Christopher et al. 2012).

N.H. Truong • P. Van Pham (*)

Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam e-mail: This email address is being protected from spam bots, you need Javascript enabled to view it

© Springer International Publishing AG 2017 P.V. Pham (ed.), Liver, Lung and Heart Regeneration,

Stem Cells in Clinical Applications, DOI 10.1007/978-3-319-46693-4_4

Cirrhosis is characterized by inflammation and necrosis induced by Kupffer cells and activation of hepatic satellite cells (HeSCs). Kupffer cells and HeSCs are the main types of cells which cause degeneration of liver tissue (GI-PPEUM et al.

2005). Chronic liver injury leads to the activation of HeSCs, the production of extracellular matrix components, and the secretion of proinflammatory cytokines, che- mokines and growth factors, such as transforming growth factor beta (TGF-6) (Friedman 2008). Metalloproteinase and its regulators (tissue inhibitors of metal- loproteinases; TIMPs) control the deposition and degradation of the extracellular matrix (Stefan et al. 2015).

Presently, orthotopic liver transplantation (OLT) is the priority treatment for decompensated liver cirrhosis. In most clinical studies, for many years, the percentage of surviving patients ranged from 70 to 90 % after 1 year of OLT (Abbasoglu et al. 1997; Botha et al. 2000; Busuttil et al. 1994; Sudan et al. 1998). However, patients face many obstacles, such as the high costs of OLT, high risk from invasive surgery, limitation of donor tissue, and lifelong immunosuppressive treatment (Lorenzini and Andreone 2007; Zheng and Wang 2013). Therefore, hepatocyte transplantation has emerged as a more promising alternative therapy to OLT. Hepatocyte transplantation therapy is a non-invasive method, does not require high immunity in conformity, and has full function of mature hepatocyte which accelerates recover of liver. Hepatocyte transplantation has the potential to overcome obstacles of OLT (Nussler et al. 2006). Although hepatocyte transplantation began in the 1980s, the use of therapeutic stem cells for liver cell transplantation is a recent shift.

 
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