PMID- 30979487
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20200914
IS  - 1873-2623 (Electronic)
IS  - 0041-1345 (Linking)
VI  - 51
IP  - 3
DP  - 2019 Apr
TI  - Intrasplenic Transplantation of Cytotoxic T-Lymphocyte Associated Protein 4-Fas 
      Ligand--Modified Hepatic Oval Cells for Acute Liver Injury in Rats.
PG  - 942-950
LID - S0041-1345(18)31294-6 [pii]
LID - 10.1016/j.transproceed.2019.01.060 [doi]
AB  - BACKGROUND: Intrasplenic transplantation of xenogeneic hepatic oval cells (HOCs) 
      may provide metabolic support for acute liver injury. However, xenoreactive 
      lymphocyte-mediated immune response hinders HOCs' survival in the xeno-spleen 
      parenchyma. Cytotoxic T-lymphocyte associated protein 4-Fas ligand (CTLA4.FasL), 
      a fusion product integrating 2 inhibitory elements against lymphocytes into 1 
      molecule, effectively inhibited the proliferation of allogeneic and autoimmune 
      lymphocytes. The purpose of this study was to explore the effect of CTLA4.FasL on 
      the proliferation of xenoreactive lymphocytes and evaluate the therapeutic 
      efficacy of CTLA4.FasL-modified HOC transplantation on acute liver injury in 
      rats. METHODS: The effect of CTLA4.FasL-modified mouse liver epithelial 
      progenitor cells (CTLA4.FasL-LEPCs) on the proliferation of rat lymphocytes in 
      xeno-mixed lymphocyte reaction was investigated. Furthermore, CTLA4.FasL-LEPCs 
      were intrasplenically transplanted in carbon tetrachloride- and partial 
      hepatectomy-treated rats, and the therapeutic effect was evaluated using 
      hematoxylin and eosin staining and alanine aminotransferase and aspartate 
      aminotransferase assays. The hepatocytic differentiation of CTLA4.FasL-LEPCs in 
      xenogeneic spleen was monitored by immunohistochemical staining for albumin. 
      RESULTS: In xeno-mixed lymphocyte reaction, CTLA4.FasL-LEPCs substantially 
      inhibited the rat lymphocytes proliferation. CTLA4.FasL-LEPC transplantation 
      significantly ameliorated liver injury compared with mCherry-modified LEPC and 
      LEPC transplantation, as assessed by hematoxylin and eosin staining, alanine 
      aminotransferase, and aspartate aminotransferase assays. Albumin positive cells 
      appeared only in CTLA4.FasL-LEPCs group, but not in the mCherry-modified LEPCs 
      group and LEPCs group. CONCLUSIONS: Our results indicate CTLA4.FasL-LEPCs 
      substantially improved liver function and structure in carbon tetrachloride- and 
      partial hepatectomy-induced acute liver injury rats through long-term hepatocytic 
      differentiation.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Wan, Z
AU  - Wan Z
AD  - Department of General Surgery, the First Affiliated Hospital of Nanchang 
      University, Nanchang, China. Electronic address: wanzhen011@126.com.
FAU - Wang, X
AU  - Wang X
AD  - Department of Critical Care Medicine, the First Affiliated Hospital of Nanchang 
      University, Nanchang, China.
FAU - Zhang, X
AU  - Zhang X
AD  - Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an, China.
FAU - Zhang, X
AU  - Zhang X
AD  - Department of General Surgery, the First Affiliated Hospital of Nanchang 
      University, Nanchang, China.
FAU - Chen, H
AU  - Chen H
AD  - Department of General Surgery, the First Affiliated Hospital of Nanchang 
      University, Nanchang, China.
LA  - eng
PT  - Journal Article
DEP - 20190126
PL  - United States
TA  - Transplant Proc
JT  - Transplantation proceedings
JID - 0243532
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (Ctla4 protein, rat)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Faslg protein, rat)
SB  - IM
MH  - Acute Lung Injury/metabolism/pathology/*surgery
MH  - Animals
MH  - CTLA-4 Antigen/*immunology/metabolism
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Fas Ligand Protein/*immunology/metabolism
MH  - Female
MH  - Hepatocytes/cytology/metabolism/*transplantation
MH  - Injections
MH  - Lymphocyte Activation
MH  - Lymphocyte Culture Test, Mixed
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spleen
MH  - T-Lymphocytes, Cytotoxic/*immunology
EDAT- 2019/04/14 06:00
MHDA- 2019/05/29 06:00
CRDT- 2019/04/14 06:00
PHST- 2018/10/01 00:00 [received]
PHST- 2018/12/19 00:00 [revised]
PHST- 2019/01/17 00:00 [accepted]
PHST- 2019/04/14 06:00 [entrez]
PHST- 2019/04/14 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
AID - S0041-1345(18)31294-6 [pii]
AID - 10.1016/j.transproceed.2019.01.060 [doi]
PST - ppublish
SO  - Transplant Proc. 2019 Apr;51(3):942-950. doi: 10.1016/j.transproceed.2019.01.060. 
      Epub 2019 Jan 26.