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Mesenchymal Stem Cells Prolong Survival and Prevent Lethal Complications in a Porcine Model of Fulminant Liver Failure

Mesenchymal Stem Cells Prolong Survival and Prevent Lethal Complications in a Porcine Model of Fulminant Liver Failure

Niang-Cheng Lin, Hao-Hsiang Wu, Jennifer Hui-Chun Ho, Chin-Su Liu, Oscar Kuang-Sheng Lee

Xenotransplantation. 2019 Nov;26(6):e12542.

PMID: 31219208

Abstract:

Background:
Fulminant liver failure (FLF) is a life-threatening disease.
Methods:
Lethal FLF was induced by ischemia-reperfusion (I-R) injury in mini-pigs, and MSCs were infused via splenic vein after reperfusion.
Results:
Accumulated survival within 28 days was significantly improved by MSCs (P = 0.0348). Notably, MSCs maintained blood-gas homeostasis in the first 24 hours and prevented FLF-induced elevation of prothrombin time, international normalized ratio, and creatinine and ammonia levels in the first 3 days. With MSCs, serum levels of liver enzymes gradually decreased after 3 days, and platelet count was back to normal at 1 week of FLF. MSCs promoted liver regeneration within 2 weeks and differentiated into functional hepatocytes at 2-4 weeks after transplantation, evidenced by increase in Ki67-positive cells, detectable human hepatocyte growth factor, human vascular endothelial growth factor, human hepatocyte-specific antigen, and human albumin-expressing cells in the liver at different time points. Reactive oxidative species (ROS) were accumulated after FLF and eliminated at 4 weeks after MSC transplantation.
Conclusions:
Together, MSCs prolong the survival and prevent lethal sequelae of I-R injury-induced FLF by maintenance of liver-function homeostasis and rescue of ROS in the acute stage and by homing and differentiation into hepatocytes in the subacute stage.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP127464602	Vascular Endothelial Growth Factor human		127464-60-2	Price
IAR4248594	Hepatocyte Growth Factor human			Price

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