Secretome from human adipose-derived stem cells protects mouse liver from hepatic ischemia–reperfusion injury

Abstract

Despite widespread interest in stem cells, their clinical application is largely limited owing to safety and cost concerns. We intended to overcome these limitations by evaluating whether the secretome of human adipose tissue-derived stem cells (ASCs) could be used to reverse ischemia/reperfusion (IR) injury in mice. After establishment of hepatic IR injury in BALB/c mice, the mice were infused with saline solution (saline group), 1.0 × 10⁶ human ASCs (ASC group), 25-fold-concentrated ASC-conditioned medium (ASC-secretome group), which was the same volume as used for the ASC infusion, or concentrated control medium (medium-only group). After reperfusion, we obtained serum and liver specimens and compared parameters reflecting the degree of injury and mechanisms between the groups. At 6 hours after reperfusion, serum interleukin (IL)-6 levels were decreased in both ASC and ASC-secretome groups (P < .05). At 12 and 24 hours after reperfusion, both ASC and ASC-secretome groups also demonstrated lesser histologic scores than did their controls (P < .05). In addition, the decreases in the expression of the cell adhesion markers intercellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1 and in neutrophil infiltration into the liver were noted in the ASC-secretome group as well as in the ASC group. ASC and ASC-secretome infusions both alleviated liver damage and improved the liver microenvironment after hepatic IR injury. Our results indicate that the therapeutic potential of ASCs may result from a paracrine effect mediated by the ASC secretome; our work suggests a novel secretome-based therapeutic strategy to treat hepatic IR injury.