Define mesenchymal stem cell from its fate:Biodisposition of human mesenchymal stem cells in normal and Con-A induced liver injury mice.

The pharmaceutical industry and clinical trials have been revolutionized mesenchymal stem cell-based therapeutics. However, little has the pharmacokinetics of transplanted cells been characterized in their target tissues under healthy or disease condition. A qPCR analytical method with matrix effect was developed to track the biodistribution of human mesenchymal stem cells in normal and Con A induced liver injury mice. MSC disposition in blood and different organs were compared and relevant PK parameters were calculated. Human and mice MSCs (hMSCs and mMSCs) displayed a very similar pharmacokinetic profile in all tested doses: about 95% of the detected hMSCs accumulated in the lung, 3% in the liver, while almost negligible cells were detected in other tissues. A significant double peak of hMSCs concentration emerged in the lung within 1-2 hours after intravenous injection, so did the mMSCs. Prazosin, a vasodilator could eliminate the second peak in the lung and increase its Cmax and AUC by 10% in the first 2 hours. The injury caused by Con A was significantly reduced by hMSCs while the Cmax and AUC0-8 of cells in the injured liver was decreased by 54% and 50% respectively. And the Cmax and AUC would be improved with the alleviation of congestion through the administration of heparin. The study provides a novel insight into the pharmacokinetics of exogenous MSCs in normal and Con-A induced liver injury mice which provided a framework for optimizing cell transplantation. Significance Statement MSCs are known for their potential as regenerative therapies in treating several diseases, while an insufficient understanding of the pharmacokinetics of MSCs restricts their future application. The current study was the first time to elucidate the PK and the possible factors including dosage, species and derived sources, disease in a systematic way. Furthermore, we investigated that ConA-induced liver injury significantly prevent cells from entering injury site which could be reversed by the diminished congestion achieved by heparin.