Human mesenchymal stem cells (MSC) indirectly preserve liver of irradiation damage

Abstract

The present work was initiated in an effort to evaluate the potential therapeutic contribution of the infusion of MSC for the correction of liver injuries. We subjected NOD-SCID mice to a 10.5 Gy abdominal irradiation and we tested the biological and histological markers of liver injury in the absence and after infusion of expanded human MSC. Irradiation alone induced a significant elevation of transaminases (ALT and AST). Apoptosis in the endothelial layer of vessels was observed. When MSC were infused in mice, a significant decrease of transaminases was measured, and a total disappearance of apoptotic cells. MSC were not found in liver. To explain the protection of liver without MSC engraftment, we hypothesize an indirect action of MSC on the liver via the intestinal tract. Pelvic or total body irradiation induces intestinal absorption defects leading to an alteration of the enterohepatic recirculation of bile acids. This alteration induces an increase in Deoxy Cholic Acid (DCA) which is hepatoxic. In the present study, we confirm these results. DCA concentration increased approximately 2-fold after irradiation but stayed to the baseline level after MSC injection. We propose from our observations that, following irradiation, MSC infusion indirectly corrected liver dysfunction by preventing gut damage. This explanation would be consistent with the absence of MSC engraftment in liver. These results evidenced that MSC treatment of a target organ may have an effect on distant tissues. This observation comes in support to the interest for the use of MSC for cellular therapy in multiple pathologies proposed in the recent years. © Mouiseddine et al