Transplantation of Mesenchymal Stem Cells Attenuates Acute Liver Failure in Mice via an Interleukin-4-dependent Switch to the M2 Macrophage Anti-inflammatory Phenotype

Wear particles from total joint arthroplasties (TJAs) induce chronic inflammation, macrophage infiltration and lead to bone loss by promoting bone destruction and inhibiting bone formation. Inhibition of particle-associated chronic inflammation and the associated bone loss is critical to the success and survivorship of TJAs. The purpose of this study is to test the hypothesis that polyethylene particle induced chronic inflammatory bone loss could be suppressed by local injection of NF-κB sensing Interleukin-4 (IL-4) over-expressing MSCs using the murine continuous polyethylene particle infusion model. The animal model was generated with continuous infusion of polyethylene particles into the intramedullary space of the femur for 6 weeks. Cells were locally injected into the intramedullary space 3 weeks after the primary surgery. Femurs were collected 6 weeks after the primary surgery. Micro-computational tomography (μCT), histochemical and immunohistochemical analyses were performed. Particle-infusion resulted in a prolonged pro-inflammatory M1 macrophage dominated phenotype and a decrease of the anti-inflammatory M2 macrophage phenotype, an increase in TRAP positive osteoclasts, and lower alkaline phosphatase staining area and bone mineral density, indicating chronic particle-associated inflammatory bone loss. Local injection of MSCs or NF-κB sensing IL-4 over-expressing MSCs reversed the particle-associated chronic inflammatory bone loss and facilitated bone healing. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments, which could be an efficacious therapeutic strategy for periprosthetic osteolysis.

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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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