IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression

Background. Mesenchymal stem cells (MSCs), with the powerful metabolic and functional supporting abilities for inflammatory diseases, may be an effective therapeutic strategy for acute liver failure (ALF). However, the efficacy of MSCs can still be promoted if pretreatment is applied to enhance their poor migration towards the damaged liver. The purpose of this study is to determine the effect of IL-1β pretreatment on the efficacy and homing ability of MSCs in ALF. Methods. MSCs were isolated by the whole bone marrow adherence method and characterized. The efficacy and homing ability of IL-1β-pretreated MSCs (Pre-MSCs) were examined in a rat ALF model and compared with that of MSCs and normal saline. Then, Western blot was performed to detect the c-Met and CXCR4 expression of MSCs and Pre-MSCs and followed by flow cytometry to detect the meaningful indicators. Finally, the migration abilities of different cells and different conditions were tested by the Transwell migration assay. Results. MSCs of ideal purity were successfully isolated and cultured. Comparing with MSCs, Pre-MSCs had significantly better efficacy on improving the survival rate and liver function of ALF rats. Further analyses of damaged liver tissues showed that IL-1β pretreatment significantly enhanced the efficacy of MSCs on suppressing liver necrosis. Besides, Pre-MSCs exhibited better effects in inhibiting apoptosis and activating proliferation. The results of tracing experiments with CM-Dil-labeled cells confirmed that more cells migrated to the damaged liver in the Pre-MSC group. In terms of mechanism, the CXCR4 expression was significantly enhanced by IL-1β pretreatment, and an increased migration ability towards SDF-1 that could be reversed by AMD3100 was found in Pre-MSCs. Conclusion. IL-1β pretreatment could enhance the homing ability of MSCs at least partially by increasing the expression of CXCR4 and further improve the efficacy of MSCs on ALF.

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Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acetaminophen-induced acute liver failure through activating ERK and IGF-1R/PI3K/AKT signaling pathway

Journal of Pharmacological Sciences ◽

10.1016/j.jphs.2021.06.008 ◽

2021 ◽

Author(s):

Han-You Wu ◽

Xiang-Cheng Zhang ◽

Bing-Bing Jia ◽

Ye Cao ◽

Kai-Yan ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Failure ◽

Acute Liver Failure ◽

Signaling Pathway ◽

Umbilical Cord ◽

Akt Signaling ◽

Human Umbilical Cord ◽

Akt Signaling Pathway

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VEGF 165 gene‐modified human umbilical cord blood mesenchymal stem cells protect against acute liver failure in rats

The Journal of Gene Medicine ◽

10.1002/jgm.3369 ◽

2021 ◽

Author(s):

Haiou Chen ◽

Shigang Tang ◽

Jinmao Liao ◽

Meng Liu ◽

Yihe Lin

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Failure ◽

Acute Liver Failure ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Human Umbilical Cord Blood ◽

Human Umbilical Cord

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Exosomes derived from human umbilical cord mesenchymal stem cells alleviate acute liver failure by reducing the activity of the NLRP3 inflammasome in macrophages

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.11.189 ◽

2019 ◽

Vol 508 (3) ◽

pp. 735-741 ◽

Cited By ~ 23

Author(s):

Linrui Jiang ◽

Shuqin Zhang ◽

Huazhong Hu ◽

Jing Yang ◽

XiaoYan Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Failure ◽

Acute Liver Failure ◽

Umbilical Cord ◽

Nlrp3 Inflammasome ◽

Human Umbilical Cord

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Interleukin-10 secreted by mesenchymal stem cells attenuates acute liver failure through inhibiting pyroptosis

Hepatology Research ◽

10.1111/hepr.12969 ◽

2017 ◽

Vol 48 (3) ◽

pp. E194-E202 ◽

Cited By ~ 23

Author(s):

Jinglin Wang ◽

Haozhen Ren ◽

Xianwen Yuan ◽

Hucheng Ma ◽

Xiaolei Shi ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Failure ◽

Acute Liver Failure ◽

Interleukin 10

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Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure

BMC Medicine ◽

10.1186/1741-7015-10-56 ◽

2012 ◽

Vol 10 (1) ◽

Cited By ~ 57

Author(s):

Hongcui Cao ◽

Jinfeng Yang ◽

Jiong Yu ◽

Qiaoling Pan ◽

Jianzhou Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Failure ◽

Acute Liver Failure ◽

Therapeutic Potential ◽

Miniature Pigs ◽

Placental Mesenchymal Stem Cells

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Prostaglandin E 2 secreted by mesenchymal stem cells protects against acute liver failure via enhancing hepatocyte proliferation

The FASEB Journal ◽

10.1096/fj.201801349rr ◽

2018 ◽

Vol 33 (2) ◽

pp. 2514-2525 ◽

Cited By ~ 6

Author(s):

Yang Liu ◽

Haozhen Ren ◽

Jinglin Wang ◽

Faji Yang ◽

Jun Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Failure ◽

Acute Liver Failure ◽

Hepatocyte Proliferation ◽

Prostaglandin E

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Therapeutic Effect of Human Umbilical Cord Mesenchymal Stem Cells at Various Passages on Acute Liver Failure in Rats

Stem Cells International ◽

10.1155/2018/7159465 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Yongting Zhang ◽

Yuwen Li ◽

Wenting Li ◽

Jie Cai ◽

Ming Yue ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Liver Failure ◽

Acute Liver Failure ◽

Umbilical Cord ◽

Therapeutic Potential ◽

Human Umbilical Cord ◽

Sd Rats ◽

Recipient Liver ◽

Injured Liver

Recent studies have described beneficial effects of an infusion of mesenchymal stem cells (MSCs) derived from Wharton’s jelly tissue, for the treatment of acute liver failure (ALF). However, data on the therapeutic potential of culture-expanded MSCs are lacking. We examined the therapeutic potential of passage five (P5) and ten (P10) human umbilical cord- (hUC-) MSCs via their transplantation into Sprague-Dawley (SD) rats with D-galactosamine (D-GalN) and LPS-induced acute liver failure (ALF). SD rats were randomly divided into three groups: control group, P5 hUC-MSCs group, and P10 hUC-MSCs group. After transplantation, P5 hUC-MSCs provided a significant survival benefit. The analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) levels showed that transplantation with P5 hUC-MSCs was more effective than treatment with P10 hUC-MSCs. P5 hUC-MSCs also successfully downregulated the hepatic activity index (HAI) scores. Compared to P10 hUC-MSCs in vivo, P5 hUC-MSCs significantly enhanced the regeneration and inhibited the apoptosis of hepatocytes. CM-Dil-labeled hUC-MSCs were found to engraft within the recipient liver, whereas the homing of cells to the recipient liver in the P10 hUC-MSCs group was less effective compared to the P5 hUC-MSCs group. Previous studies have shown that the concentration of hepatocyte growth factor (HGF) in the injured liver was significantly increased. HGF is commonly known as the ligand of c-Met. The level of c-Met in hUC-MSCs as detected by Western blotting indicated that at a higher passage number, there is a decrease in c-Met. These data suggest that direct transplantation of P5 hUC-MSCs can more efficiently home to an injured liver. Subsequently, the P5 hUC-MSCs can rescue ALF and repopulate the livers of rats through the stimulation of endogenous liver regeneration and inhibition of hepatocellular apoptosis for compensated liver function, which is dependent on the higher level of c-Met than P10 hUC-MSCs.

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