Immunomodulatory effects of mesenchymal stem cells derived from adipose tissues in a rat orthotopic liver transplantation model.
BACKGROUND
Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find a safe and effective method for preventing and treating rejection. This study was designed to confirm the immunomodulatory effects of rat mesenchymal stem cells (MSCs) in vitro and investigate the tolerogenic features in a rat model of allogeneic liver transplantation.


METHODS
MSCs were isolated from adipose tissue of Sprague-Dawley (SD) rats and cultured. In vitro, MSCs were added into a mixed lymphocyte culture (MLC) system to study the inhibitory effects of MSCs on the proliferation of T lymphocytes in Wistar rats. By using SD and Wistar rats as liver donors and recipients, an orthotopic liver transplantation model was established and the rats were divided into a MSC-treated group and a blank control group. On postoperative day 7, all rats were sacrificed, and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured. The pathological changes of liver tissue and apoptosis of hepatocytes were also assessed.


RESULTS
In in vitro MLC, T lymphocyte proliferation in Wistar rats was significantly inhibited by 48.44%. In the MSC-treated group, the levels of ALT, AST, TBIL, IL-2 and IL-10 were 134.2+/-45.0 U/L, 162.5+/-30.5 U/L, 30.6+/-5.4 micromol/L, 187.35+/-18.26 microg/L and 193.95+/-37.62 microg/L, and those in the blank control group were 355.6+/-54.3 U/L, 296.4+/-71.2 U/L, 145.7+/-28.6 micromol/L, 295.73+/-57.15 microg/L and 75.12+/-11.23 microg/L, respectively, with statistically significant differences (P<0.05). Pathological examination revealed that the rejection in the MSC-treated group was clearly alleviated compared with that in the blank control group. TUNEL indicated that the apoptosis of hepatocytes in the MSC-treated group was milder than that in the blank control group (P<0.05).


CONCLUSIONS
Adipose-derived MSCs clearly inhibit recipient-derived T lymphocyte proliferation in MLC and significantly alleviate acute rejection following orthotopic liver transplantation in rats.
Wan
Chi-Dan
CD
Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. chidanwan@163.com
Cheng
Rui
R
Wang
Hong-Bo
HB
Liu
Tao
T
D000208:Acute Disease; D000273:Adipose Tissue / Q000166:cytology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007108:Immune Tolerance / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008099:Liver / Q000276:immunology / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014184:Transplantation, Homologous
D007155:Immunologic Factors; D007376:Interleukin-2; D016753:Interleukin-10; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin