Steroid-Mediated Decrease in Blood Mesenchymal Stem Cells in Liver Transplant could Impact Long-Term Recovery

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...

Full description

Saved in:
Bibliographic Details
Published in:Stem cell reviews and reports 2017-10, Vol.13 (5), p.644-658
Main Authors: Walker, Nykia D, Mourad, Yasmine, Liu, Katherine, Buxhoeveden, Michael, Schoenberg, Catherine, Eloy, Jean D, Wilson, Dorian J, Brown, Lloyd G, Botea, Andrei, Chaudhry, Faraz, Greco, Steven J, Ponzio, Nicholas M, Pyrsopoulos, Nikolaos, Koneru, Baburao, Gubenko, Yuriy, Rameshwar, Pranela
Format: Article
Language:English
Subjects:
Blood
Case-Control Studies
Cell Count
Cell Movement - drug effects
Chemokine CXCL12 - genetics
Chemokine CXCL12 - immunology
Culture
CXCL12 protein
CXCR4 protein
Cytokines
Cytoskeleton
End Stage Liver Disease - genetics
End Stage Liver Disease - immunology
End Stage Liver Disease - pathology
End Stage Liver Disease - surgery
Gene Expression Regulation
Graft rejection
Graft Rejection - immunology
Graft Rejection - pathology
Graft Rejection - prevention & control
Hepatocytes
Humans
Immunosuppressive Agents - pharmacology
Inflammation
Liver
Liver - metabolism
Liver - pathology
Liver - surgery
Liver diseases
Liver Transplantation
Liver transplants
Mesenchymal Stem Cell Transplantation
Mesenchymal stem cells
Mesenchymal Stem Cells - drug effects
Mesenchymal Stem Cells - immunology
Mesenchymal Stem Cells - pathology
Mesenchyme
Methylprednisolone - pharmacology
Migration
Primary Cell Culture
Receptors, CXCR4 - genetics
Receptors, CXCR4 - immunology
Recovery of Function - physiology
Signal Transduction
Stem cells
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2629-3269
2629-3277
DOI:10.1007/s12015-017-9751-3