Mesenchymal stem cells accelerate liver regeneration in acute liver failure animal model

Abstract

Introduction: The massive hepatic necrosis of acute liver failure (ALF) results in a sudden loss of hepatic cells. Although most hepatocyte cells of ALF are completely lost, stem cell-derived circulating cells and endogenous progenitor cells rapidly regenerate them. Mesenchymal stem cells (MSCs) have a critical role in the regeneration of liver injury through regulating platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) levels. However, their fluctuating levels in the healing process and correlation to the decrease of liver function markers remain unclear. The aim of this study was to analyze the effects of MSCs in accelerating liver regeneration of ALF by measuring VEGF and PDGF levels on day 2 and 7, as well as SGPT and SGOT levels, and assessing histopathology appearance.
 Methods: Using an ALF rat model, 12 animals were randomly assigned into two groups: umbilical cord (UC)-MSC injection (T1) and vehicle control (Veh). ELISA assay was employed to measure PDGF and VEGF levels, an automatic analyzer was used to assess serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT), and hematoxylin and eosin (H&E) staining was used to evaluate morphological appearance.
 Results: The study showed an significant (P<0.001) increase of PDGF and VEGF levels on the 2nd day, followed by a decrease on the 7th day, along with a decrease of SGPT and SGOT levels as well as the normality of histology appearance.
 Conclusion: In conclusion, administration of MSCs may accelerate liver regeneration of ALF through PDGF and VEGF regulation.

The Role of Hypoxic Mesenchymal Stem Cells Conditioned Medium in Increasing Vascular Endothelial Growth Factors (VEGF) Levels and Collagen Synthesis to Accelerate Wound Healing

“…The cells were rinsed in PBS and fixed with cold 70% ethanol (v/v) for 1 hour at room temperature, then rinsed three times with twice-distilled water. A volume of 1 mL 2% Alizarin Red solution (w/v) (pH 4.1-4.3) was added and the cells incubated for 30 minutes at a room temperature, then rinsed four times in twice-distilled water (Putra, et al, 2018).…”

“…Recently, some studies showed VEGF could stimulate vascular permeability, adhesion molecule expression, and granulation tissue formation to strengthen the healed wound (Johnson & Wilgus, 2014;Putra, et al, 2018). In regard to mediate a collagen synthesis, the VEGF used the PI3K/Akt pathway to activate fibroblast into myofibroblast (Lu, et al, 2010).…”

Perspective of placenta derived mesenchymal stem cells in acute liver failure

“…Hepatic failure is a disastrous consequence of liver loss, in which the repair of residual hepatocytes is not performed in a timely and appropriate manner, resulting in increased mortality [103]. Massive hepatic necrosis in acute liver failure [97] is caused by sudden loss of hepatocytes due to a variety of acute injuries induced by hepatotoxic drugs, immune system attack, and viral infections [104][105][106]. While most hepatocytes are completely destroyed in ALF, the circulating Bone Marrow-derived cells and endogenous hepatocyte progenitor cells can rapidly regenerate the liver [107].…”

“…1. PD-MSCs are recruited to the damaged area by VCAM-1 and VLA-4 adhesion molecules [104,110,111] affecting the remaining hepatocytes through cell-cell contact and secretion of TGF-α, EGF, HGF, and VEGF tropic factors [112,113].…”

“…MSCs play a critical role in liver regeneration because of their ability to produce and regulate platelet-activating factor (PAF), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) [104]. Several studies have demonstrated the significance of MSCs in liver diseases.…”