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

被引:4
作者
Walker, Nykia D. [1 ,2 ]
Mourad, Yasmine [2 ]
Liu, Katherine [3 ]
Buxhoeveden, Michael [3 ]
Schoenberg, Catherine [3 ]
Eloy, Jean D. [3 ]
Wilson, Dorian J. [4 ]
Brown, Lloyd G. [4 ]
Botea, Andrei [3 ]
Chaudhry, Faraz [3 ]
Greco, Steven J. [1 ]
Ponzio, Nicholas M. [5 ]
Pyrsopoulos, Nikolaos [1 ]
Koneru, Baburao [4 ]
Gubenko, Yuriy [3 ]
Rameshwar, Pranela [1 ,2 ]
机构
[1] Rutgers New Jersey Med Sch, Div Hematol Oncol, Dept Med, Newark, NJ 07103 USA
[2] Rutgers Grad Sch Biomed Sci, Newark, NJ 07103 USA
[3] Rutgers New Jersey Med Sch, Dept Anesthesiol, Newark, NJ 07103 USA
[4] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ USA
[5] Rutgers New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ USA
关键词
Chemokine; Inflammation; Regenerative medicine; Liver; Transplant; Stemcell; Glucocorticoid; Mesenchymal stem cells; Steroid; HEPATITIS-B-VIRUS; STROMAL CELLS; PROGENITOR CELLS; BONE-MARROW; REGENERATION; THERAPY; DISEASE; MIGRATION; CANCER; IMMUNOSUPPRESSION;
D O I
10.1007/s12015-017-9751-3
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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.
引用
收藏
页码:644 / 658
页数:15
相关论文
共 46 条
[1]   Sirolimus: More cause for alarm? [J].
Agarwal, Parul D. ;
Lucey, Michael R. .
LIVER TRANSPLANTATION, 2012, 18 (09) :1003-1004
[2]   Antigen-presenting property of mesenchymal stem cells occurs during a narrow window at low levels of interferon-γ [J].
Chan, Jennifer L. ;
Tang, Katherine C. ;
Patel, Anoop P. ;
Bonilla, Larissa M. ;
Pierobon, Nicola ;
Ponzio, Nicholas M. ;
Rameshwar, Pranela .
BLOOD, 2006, 107 (12) :4817-4824
[3]   Mesenchymal stem cells showed the highest potential for the regeneration of injured liver tissue compared with other subpopulations of the bone marrow [J].
Cho, Kyung-Ah ;
Ju, Sun-Young ;
Cho, Su Jin ;
Jung, Yun-Jae ;
Woo, So-Youn ;
Seoh, Ju-Young ;
Han, Ho-Seong ;
Ryu, Kyung-Ha .
CELL BIOLOGY INTERNATIONAL, 2009, 33 (07) :772-777
[4]   Mesenchymal Stem Cells in Early Entry of Breast Cancer into Bone Marrow [J].
Corcoran, Kelly E. ;
Trzaska, Katarzyna A. ;
Fernandes, Helen ;
Bryan, Margarette ;
Taborga, Marcelo ;
Srinivas, Venkatesh ;
Packman, Kathryn ;
Patel, Prem S. ;
Rameshwar, Pranela .
PLOS ONE, 2008, 3 (06)
[5]   The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights [J].
Coutinho, Agnes E. ;
Chapman, Karen E. .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2011, 335 (01) :2-13
[6]   Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy? [J].
De Becker, Ann ;
Van Riet, Ivan .
WORLD JOURNAL OF STEM CELLS, 2016, 8 (03) :73-87
[7]   The role of hepatocytes and oval cells in liver regeneration and repopulation [J].
Fausto, N ;
Campbell, JS .
MECHANISMS OF DEVELOPMENT, 2003, 120 (01) :117-130
[8]   Stem cell therapy for chronic liver disease - choosing the right tools for the job [J].
Forbes, Stuart J. .
GUT, 2008, 57 (02) :153-155
[9]   Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury [J].
Friedman, SL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (04) :2247-2250
[10]  
Greco SJ, 2011, AM J CANCER RES, V1, P701