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

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 human MSC (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 separately. The increase of hMSCs exposure in the liver (AUC liver 0 – 72 hour ) were more significant in ALI than in CLF (177.1% versus 96.2%). In the ALI model, the hMSCs exposures in the lung (AUC lung 0 – 72 hour ) increased by nearly 50%, whereas it 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 depletionofNK cells could increasehMSCs 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.

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