Intravenous human mesenchymal stem cells transplantation in NOD/SCID mice preserve liver integrity of irradiation damage
Résumé
This work was initiated in an effort to evaluate the potential therapeutic contribution of the infusion of mesenchymal stem cells (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 the 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 this study, we confirm these results. DCA concentration increased approximately twofold 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. © 2012 Springer Science+Business Media, LLC.
Mots clés
alanine aminotransferase
aspartate aminotransferase
bile acid
analysis of variance
animal
article
blood
evaluation
flow cytometry
histology
human
liver
mesenchymal stem cell transplantation
methodology
mouse
mouse mutant
nick end labeling
nonobese diabetic mouse
pathology
radiation exposure
radiation injury
real time polymerase chain reaction
Alanine Transaminase
Analysis of Variance
Animals
Aspartate Aminotransferases
Bile Acids and Salts
Flow Cytometry
Histological Techniques
Humans
In Situ Nick-End Labeling
Liver
Mesenchymal Stem Cell Transplantation
Mice
Inbred NOD
SCID
Radiation Injuries
Experimental
Real-Time Polymerase Chain Reaction
Mus