Mesenchymal Stem Cell Fates in Murine Acute Liver Injury and Chronic Liver Fibrosis Induced by Carbon Tetrachloride

Abstract

Mesenchymal stem cells (MSCs) therapy has shown potential benefits in multiple diseases. However, their clinic performance is not as satisfactory as expected. This study aimed to provide an alternative explanation by comparing MSCs' fates in different liver diseases. The distribution and therapeutic effects of hMSCs were investigated in acute liver injury (ALI) and chronic liver fibrosis (CLF) mice models, respectively. The two models were induced by single or repeated injection of carbon tetrachloride (CCl 4 ) separately. The increase of hMSCs exposure in the liver (AUC liver 0-72 h ) were more significant in ALI than in CLF (177.1% vs. 96.2%). In the ALI model, the hMSCs exposures in the lung (AUC lung 0-72 h ) increased by nearly 50% while decreased by 60.7% in CLF. The efficacy satellite study indicated that hMSCs could significantly ameliorate liver injury in ALI, but its effects in CLF were limited.In the ALI, suppressed Natural Killer (NK) cell activities were observed, while NK cell activities were increased in CLF. The depletion of NK cells could increase hMSCs exposure in mice. For mice MSC (mMSCs), their cell fates in ALI were very similar to hMSCs in ALI: mMSCs' exposure in the liver and lung increased in ALI. In conclusion, our study revealed the distinct cell pharmacokinetic patterns of MSCs in ALI and CLF mice, which might be at least partially attributed to the different NK cell activities in the two liver diseases. This finding provided a novel insight into the varied MSCs' therapeutic efficacy in the clinic.

State-of-the-Art and Future Directions in Organ Regeneration with Mesenchymal Stem Cells and Derived Products during Dynamic Liver Preservation

“…In the setting of liver disease, the beneficial effects of MSCs have been demonstrated in a large number of preclinical studies that investigated their effects in both acute and chronic disease models [46][47][48][49][50][51], eventually leading to their administration to humans suffering from cirrhosis and liver failure [52] (Table 2).…”