ABSTRACT
Objective@#To investigate the protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A (ConA)-induced acute liver injury in mice.@*Methods@#A total of 88 male C57BL/6 mice were randomly divided into normal control group (group C), ConA model group (group M), and human liver-derived stem cells (HYX1)+ConA group (group E); according to the interval between phosphate buffer/HYX1 injection and ConA injection, Groups M and E were further divided into 3-hour groups (M1 and E1 groups), 6-hour groups (M2 and E2 groups), 12-hour groups (M3 and E3 groups), 24-hour groups (M4 and E4 groups), and 48-hour groups (M5 and E5 groups). The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin (TBil) in peripheral blood were measured, liver tissue sections were used to observe pathological changes, and the Ishak score for liver inflammation was determined. The independent samples t-test was used for comparison between groups, and P < 0.05 was considered statistically significant.@*Results@#The levels of ALT, AST, and TBil in group C were (36.25±1.16) U/L, (120.20±5.77) U/L, and (2.20±0.23) μmol/L, respectively; the levels of ALT, AST, and TBil and Ishak score were (8 721.23±837.39) U/L, (8 110.31±290.10) U/L, (8.41±0.10) μmol/L, and (13.32±1.30), respectively, in group M1, (8 334.31±666.50) U/L, (7 560.20±760.34) U/L, (10.40±0.80) μmol/L, and (12.67±0.81), respectively, in group M2, (8 960.75±551.93) U/L, (8 535.62±675.14) U/L, (10.95±1.43) μmol/L, and (14.57±0.65), respectively, in group M3, (8 618.57±886.40) U/L, (11 440.54 ± 1 327.86) U/L, (13.30±1.86) μmol/L, and (13.21±1.06), respectively, in group M4, and (10 170.13±1 112.37) U/L, (11 470.56±1 108.40) U/L, (12.75±1.55) μmol/L, and (15.07±1.58), respectively, in group M5. The levels of ALT, AST, and TBil and Ishak score were (1 016.35±163.47) U/L, (952.30±103.91) U/L, (7.77±0.62) μmol/L, and (3.50±0.21), respectively, in group E1, (42.10±6.20) U/L, (126.72±13.33) U/L, (3.41±0.53) μmol/L, and (2.01±0.40), respectively, in group E2, (44.21±4.30) U/L, (216.71±35.88) U/L, (3.47±0.44) μmol/L, and (2.13±0.25), respectively, in group E3, (2 909.69±212.14) U/L, (2 988.43±333.70) U/L, (7.03±0.93) μmol/L, and (4.70±0.50), respectively, in group E4, and (7 874.26±799.60) U/L, (10 940.54±947.35) U/L, (10.53±1.09) μmol/L, and (8.60±0.83), respectively, in group E5. Groups M1-M5 had significantly higher levels of ALT, AST, and TBil than group C (all P < 0.01), and groups M1-M4 had significantly higher levels of AST and ALT than groups E1-E4 (all P < 0.01), while there were no significant differences in the levels of AST and ALT between groups M5 and E5 (both P > 0.05). The pathological sections of liver tissue showed that compared with group M, group E had significant reductions in the degree of necrosis and Ishak score (both P < 0.05).@*Conclusion@#Intraperitoneal transplantation of human liver-derived stem cells has a protective effect against ConA-induced acute liver injury in mice, and the injection at 6 and 12 hours in advance has the best protective effect.
ABSTRACT
Stem cell has been one of the focuses in current biomedical research. It has been well documented that there are various liver stem cells (LSCs) with different markers in liver, and they play important roles in liver regeneration. Moreover, some progresses have been made in autologous and allogeneic stem cells transplantation for the treatment of end-stage liver diseases. However, the origin and markers of LSCs have not been fully clarified, and the mechanism involved in LSCs proliferation and differentiation remains to be deeply studied. With the improvements of lineage tracing technique and stem cell isolation and culture system, it is believed that the origin of LSCs and their role in liver regeneration will be further clarified, and LSCs treatment for liver diseases will soon become a reality.
ABSTRACT
Liver stem cells are primitive cells with self-renewing capacity and bidirectional differentiation potential to differentiate into mature hepatocytes or biliary epithelial cells. Liver stem cells not only play roles in the homeostasis maintenance, injury repair and regeneration of liver, but also have huge potential applications in cell therapy of liver diseases, construction of bioartificial liver and liver-oriented gene therapy. In this review, we summarized the major types of liver stem cells, as well as their origins and molecular markers.
ABSTRACT
Objective To optimize the method of isolating ,culturing and screening fetal mouse liver stem cells in vitro ,and to identify the potential of bi‐directional differentiation .Methods The fetal liver stem cells of mouse were isolated by the density gra‐dient centrifugation and cell difference adherence method ,the proliferation of stem cells was determined by cell plate cloning tech‐nique and MTT method;stem cells were induced for differentiation by adding DMSO and HGF .Results The isolated stem cells showed adherence within 24 h ,which were orbicular‐ovate ,closely packed ,activated within 1~2 weeks ;the positive rates of CD133 , CD49f and EPCAM were (97 .95 ± 1 .21)% ,(92 .71 ± 3 .49)% and (50 .73 ± 3 .45)% respectively ;AFP and CK19 proteins were expressed;red glycogen granules were seen by PAS after induced differentiation;ALB and HNF‐4αwere expressed .Conclusion Fe‐tal hepatic stem cells are successfully isolated by the density gradient centrifugation combined with difference adherence method ,and the isolated cells have strong stemness and proliferation ability ,as well as the ability of bi‐directional differentiation towards hepato‐cytes and bile duct epithelial cells .
ABSTRACT
The hypothesis that tumor comes from stem cells has been demonstrated in various human tumors.Cancer is not only a genetic disease but also a stem cell disease. It is a key to regeneration, mutations and recurrence of tumors that gene mutations affect stem cells, and then stem cells mutate to cancer stem cells. In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas(HCC)arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells?More recently, there is a hypothesis that HCC arise from maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties(ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.
ABSTRACT
Delta-like ligand 4(Dll4), one ligand of Notch receptors, is highly expressed in tumour vessels and is negative regulator in tumour angiogenesis. Blocking Dll4/Notch sinaling could promote tumour angiogenesis, whereas due to poor perrusion of newly forming vessels, tumour growth is inhibited, which is effective even to the tumour patients unresponsive to blocking vascular endothelial growth factor pathway. So, Dll4 is becoming a new promising target in anti-tumour theraties.
ABSTRACT
Liver stem cells (LSCs) have the abilities of self-renewal, proliferation and differentiating to hepatocytes and bile duct epitheliums. LSCs research becomes a hotspet in liver diseases research areas now-adays. As the research deepening, LSCs would offer a new strategy for therapies of liver diseases. This re-view summarizes liver stem cells species, resources and the application in field of liver diseases.