scholarly journals Transplantation of bone mesenchymal stem cells effectively promotes intestine regeneration to eliminate endotoxemia and reduce mortality in the animal model of acute liver failure

2020 ◽  
Author(s):  
Ting Jiang ◽  
Geng Xia ◽  
Bo Yang ◽  
Hong-wei Zhang ◽  
Yue-shan Yin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Epithelial Differentiation ◽  
Brdu Incorporation ◽  
Intestinal Epithelial ◽  
Tnf Α

Abstract Background Endotoxemia based on liver failure has been reported to be related to the worse clinical outcomes, but its management remains unsatisfactory. The addition of bone marrow mesenchymal stem cells (BMSCs) could promote the recovery of liver function and increase the survival with the liver failure. However, little is known about the potential of cell therapy with endotoxemia based on liver failure. Methods BMSCs were isolated from rats, and their morphology, differentiation potential, surface markers, and cell cycle were assayed. Thioacetamide-induced acute liver failure rats were randomized to groups with or without BMSCs. During the experiment, survival was recorded. Diamine oxidase (DAO), endotoxin, interleukin-6 (IL-6) and tumor necrosis factor- alpha (TNF-α) and tissue were analyzed by enzyme-linked immunosorbent assay (ELISA), histology, and western blot. Bromodeoxynucleoside uracil (BrdU) incorporation assay was performed to observe the migration of BMSCs. The intestinal epithelial differentiation of BMSCs was induced by co culture with small intestinal crypt in rats (IEC-6). Immunofluorescence was used to analyze the expression of intestinal endothelial markers. Western blot analysis was further performed to examine the differentiation effect when inhibiting the phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Results BrdU-traced BMSCs targeted migrate to intestinal injury sites. Mortality was significantly decreased and intestinal damage was repaired following BMSCs transplantation. Proteomics revealed higher expression of DAO, endotoxin, IL-6 and TNF-α in the model animals, but these changes were reversed after BMSCs transplantation. In the in vitro study, the intestinal epithelial differentiation of BMSCs was exhibited following co-culture. Moreover, the blocking of PI3K/AKT/mTOR signal pathway inhibited this differentiation. Conclusions These evidences indicate that BMSCs eliminate endotoxemia and reduce mortality in the animal model of acute liver failure by reducing intestine damage.

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

2017 ◽  
Vol 48 (3) ◽  
pp. E194-E202 ◽  
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

scholarly journals Melatonin-Pretreated Mesenchymal Stem Cells Improved Cognition in a Diabetic Murine Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Shaimaa Nasr Amin ◽  
Nivin Sharawy ◽  
Nashwa El Tablawy ◽  
Dalia Azmy Elberry ◽  
Mira Farouk Youssef ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Synaptic Plasticity ◽  
Object Recognition ◽  
Ex Vivo ◽  
Type I ◽  
Positive Effects ◽  
Tnf Α

Diabetes mellitus (DM) is a multisystem endocrine disorder affecting the brain. Mesenchymal stem cells (MSCs) pretreated with Melatonin have been shown to increase the potency of MSCs. This work aimed to compare Melatonin, stem cells, and stem cells pretreated with Melatonin on the cognitive functions and markers of synaptic plasticity in an animal model of type I diabetes mellitus (TIDM). Thirty-six rats represented the animal model; six rats for isolation of MSCs and 30 rats were divided into five groups: control, TIDM, TIDM + Melatonin, TIDM + Stem cells, and TIDM + Stem ex vivo Melatonin. Functional assessment was performed with Y-maze, forced swimming test and novel object recognition. Histological and biochemical evaluation of hippocampal Neuroligin 1, Sortilin, Brain-Derived Neurotrophic Factor (BDNF), inducible nitric oxide synthase (iNOS), toll-like receptor 2 (TLR2), Tumor necrosis factor-alpha (TNF-α), and Growth Associated Protein 43 (GAP43). The TIDM group showed a significant decrease of hippocampal Neuroligin, Sortilin, and BDNF and a significant increase in iNOS, TNF-α, TLR2, and GAP43. Melatonin or stem cells groups showed improvement compared to the diabetic group but not compared to the control group. TIDM + Stem ex vivo Melatonin group showed a significant improvement, and some values were restored to normal. Ex vivo melatonin-treated stem cells had improved spatial working and object recognition memory and depression, with positive effects on glucose homeostasis, inflammatory markers levels and synaptic plasticity markers expression.

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

2018 ◽  
Vol 33 (2) ◽  
pp. 2514-2525 ◽  
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

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

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
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.

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

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
He Nie ◽  
Fangmei An ◽  
Jie Mei ◽  
Cheng Yang ◽  
Qiang Zhan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Inflammatory Diseases ◽  
Cxcr4 Expression ◽  
Migration Ability ◽  
Transwell Migration Assay ◽  
Migration Assay ◽  
Effective Therapeutic Strategy

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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