Steroid-Mediated Decrease in Blood Mesenchymal Stem Cells in Liver Transplant could Impact Long-Term Recovery
Authors: Andrei Botea
Steven J Greco
Yasmine Mourad
Faraz Chaudhry
Nikolaos Pyrsopoulos
Jean D Eloy
Pranela Rameshwar
Nykia D Walker
Dorian J Wilson
Katherine Liu
Nicholas M Ponzio
Catherine Schoenberg
Baburao Koneru
Yuriy Gubenko
Michael Buxhoeveden
Lloyd G Brown
Journal: Stem Cell Reviews and Reports (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Chemokine; Glucocorticoid; Inflammation; Liver; Mesenchymal stem cells
Affiliations: Department of Medicine, Division of Hematology/Oncology, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA., Rutgers Graduate School of Biomedical Sciences, Newark, NJ, USA., Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA., Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA., Department of Pathology and Laboratory Medicine, Rutgers, New Jersey Medical School, Newark, NJ, USA., Department of Anesthesiology, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA. ., Department of Medicine, Division of Hematology/Oncology, Rutgers New Jersey Medical School, Newark, NJ, 07103, USA. ., Rutgers Graduate School of Biomedical Sciences, Newark, NJ, USA. .

Abstract:  Orthotopic liver transplant (OLT) remains the standard of care for end stage liver disease. To circumvent allo-rejection, OLT subjects receive gluococorticoids (GC). We investigated the effects of GC on endogenous mesenchymal stem (stromal) cells (MSCs) in OLT. This question is relevant because MSCs have regenerative potential and immune suppressor function. Phenotypic analyses of blood samples from 12 OLT recipients, at pre-anhepatic, anhepatic and post-transplant (2 h, Days 1 and 5) indicated a significant decrease in MSCs after GC injection. The MSCs showed better recovery in the blood from subjects who started with relatively low MSCs as compared to those with high levels at the prehepatic phase. This drop in MSCs appeared to be linked to GC since similar change was not observed in liver resection subjects. In order to understand the effects of GC on decrease MSC migration, in vitro studies were performed in transwell cultures. Untreated MSCs could not migrate towards the GC-exposed liver tissue, despite CXCR4 expression and the production of inflammatory cytokines from the liver cells. GC-treated MSCs were inefficient with respect to migration towards CXCL12, and this correlated with retracted cytoskeleton and motility. These dysfunctions were partly explained by decreases in the CXCL12/receptor axis. GC-associated decrease in MSCs in OLT recipients recovered post-transplant, despite poor migratory ability towards GC-exposed liver. In total, the study indicated that GC usage in transplant needs to be examined to determine if this could be reduced or avoided with adjuvant cell therapy. 

Retracted: No

PubPeer comments:
 Image in Figure 5b may have a repeated band, although the contrast brightness and dimensions differ. Could the authors please post the original uncropped scans? Apologies if Iu2019ve misunderstood something. *** After equalizing contrast brightness of CXCR4 7 ![file] *** Original contrast brightness ![file] , 
 OK will contact the first author for the original band Thanks , 
 #2 Is there an update on this? Acknowledgements. This work was funded by a grant from the FM Kirby Foundation. This work was performed in partial fullfilment of a doctoral thesis for NDW ,