Serum from CCl4-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis

被引:10
作者
Baig, Maria Tayyab [1 ]
Ali, Gibran [1 ]
Awan, Sana Javaid [1 ]
Shehzad, Umara [1 ]
Mehmood, Azra [1 ]
Mohsin, Sadia [2 ]
Khan, Shaheen N. [1 ]
Riazuddin, Sheikh [1 ,3 ,4 ]
机构
[1] Univ Punjab, Ctr Excellence Mol Biol, Lahore, Pakistan
[2] Temple Univ, Lewis Katz Sch Med, Cardiovasc Res Ctr, Philadelphia, PA 19122 USA
[3] Allama Iqbal Med Coll, Lahore, Pakistan
[4] SZABMU, Islamabad, Pakistan
关键词
Acute injury; preconditioning; serum; liver fibrosis; liver functions; MESENCHYMAL STEM-CELLS; FETAL BOVINE SERUM; HUMAN ADIPOSE-TISSUE; ENDOTHELIAL GROWTH-FACTOR; ACUTE-PHASE RESPONSE; HUMAN BONE-MARROW; IN-VITRO; PARTIAL-HEPATECTOMY; STROMAL CELLS; HEPATOGENIC DIFFERENTIATION;
D O I
10.1080/08977194.2017.1392945
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl4 which caused significant increase in serum levels of VEGF, SDF1 alpha and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl4-induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.
引用
收藏
页码:144 / 160
页数:17
相关论文
共 85 条
[21]  
GAULDIE J, 1990, J IMMUNOL, V144, P3804
[22]  
Gerber HP, 1999, DEVELOPMENT, V126, P1149
[23]   Adipose-derived stem cells for regenerative medicine [J].
Gimble, Jeffrey M. ;
Katz, Adam J. ;
Bunnell, Bruce A. .
CIRCULATION RESEARCH, 2007, 100 (09) :1249-1260
[24]   SDF-1/CXCR4 Axis Promotes MSCs to Repair Liver Injury Partially through Trans-Differentiation and Fusion with Hepatocytes [J].
Hao, Ning-Bo ;
Li, Chang-Zhu ;
Lu, Mu-Han ;
Tang, Bo ;
Wang, Su-Min ;
Wu, Yu-Yun ;
Liang, Guang-Ping ;
Yang, Shi-Ming .
STEM CELLS INTERNATIONAL, 2015, 2015
[25]   Adipose-Derived Stem Cells Can Abrogate Chemical-Induced Liver Fibrosis and Facilitate Recovery of Liver Function [J].
Harn, Horng-Jyh ;
Lin, Shinn-Zong ;
Hung, Shih-Hsiao ;
Subeq, Yi-Maun ;
Li, Yuan-Sheng ;
Syu, Wan-Sin ;
Ding, Dah-Ching ;
Lee, Ru-Ping ;
Hsieh, Dean-Kuo ;
Lin, Po-Cheng ;
Chiou, Tzyy-Wen .
CELL TRANSPLANTATION, 2012, 21 (12) :2753-2764
[26]  
Hatch Heather M., 2002, Cloning and Stem Cells, V4, P339, DOI 10.1089/153623002321025014
[27]  
He Y, 2011, SAUDI MED J, V32, P128
[28]   N-glycolylneuraminic acid xenoantigen contamination of human embryonic and mesenchymal stem cells is substantially reversible [J].
Heiskanen, Annamari ;
Satomaa, Tero ;
Tiitinen, Sari ;
Laitinen, Anita ;
Mannelin, Sirkka ;
Impola, Ulla ;
Mikkola, Milla ;
Olsson, Cia ;
Miller-Podraza, Halina ;
Blomqvist, Maria ;
Olonen, Anne ;
Salo, Hanna ;
Lehenkari, Petri ;
Tuuri, Timo ;
Otonkoski, Timo ;
Natunen, Jari ;
Saarinen, Juhani ;
Laine, Jarmo .
STEM CELLS, 2007, 25 (01) :197-202
[29]  
Hong H, 2004, WORLD J GASTROENTERO, V10, P2250
[30]  
Hong Tae Ho, 2013, Korean J Hepatobiliary Pancreat Surg, V17, P53, DOI 10.14701/kjhbps.2013.17.2.53