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ABSTRACT: Background
Ischemia-reperfusion injury (IRI) is commonly encountered after liver surgery. This study evaluated the hepatoprotective effects of topically applied adipose-derived mesenchymal stromal cells (ADMSCs) on hepatic IRI in a rat model.Methods
ADMSCs from transgenic green fluorescent protein Sprague-Dawley rats were topically applied to the liver surface of Sprague-Dawley rats after hepatic IRI and fixed in position by fibrin glue (group A, n = 24). An equivalent amount of ADMSCs were administered through the portal (group B, n = 24) or tail vein (group C, n = 24). In the control group (group D, n = 20), no treatment was given to the IRI liver.Results
All the rats in group A and group D survived. Within 2 days after hepatic IRI, only 50% of rats survived in group B, and ADMSCs were detected in thromboemboli within large vessels. 62.5% of the rats died in group C because most of the ADMSCs were trapped in the lungs. ADMSCs migrated across the liver capsule and homed to the injured liver parenchyma 3 days after topical application in group A. The homed ADMSCs expressed hepatocyte nuclear factor-4? and hepatocyte nuclear factor-1. Compared with group D, the rate of hepatic regeneration in group A was enhanced with less inflammation, smaller necrotic areas, and improved liver function. Proinflammatory cytokines IL-6, IL-21, and CD70 were significantly downregulated in group A by 6.3-, 2.7-, and 12.7-fold, respectively (P < 0.05). The neurogenic locus NOTCH homolog protein pathway was activated in the topical ADMSCs.Conclusions
Topically applied adipose-derived mesenchymal stromal cells demonstrated hepatoprotective effects on hepatic IRI in an animal model.
SUBMITTER: Lam PK
PROVIDER: S-EPMC5464779 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Lam Ping Kuen PK Chong Charing Ching Ning CCN Lo Anthony Wing Ip AWI Chan Anthony Wing Hung AWH Tong Cindy See Wai CSW Chin Don Wai Ching DWC Wong Kenneth Hoi Kin KHK Choy Richard Kwong Wai RKW Fung Andrew Kai-Yip AK Wang Yi Xiang YX To Ka Fai KF Lai Paul Bo San PBS
Transplantation direct 20170511 6
<h4>Background</h4>Ischemia-reperfusion injury (IRI) is commonly encountered after liver surgery. This study evaluated the hepatoprotective effects of topically applied adipose-derived mesenchymal stromal cells (ADMSCs) on hepatic IRI in a rat model.<h4>Methods</h4>ADMSCs from transgenic green fluorescent protein Sprague-Dawley rats were topically applied to the liver surface of Sprague-Dawley rats after hepatic IRI and fixed in position by fibrin glue (group A, n = 24). An equivalent amount of ...[more]