A study about immunomodulatory effect and efficacy and prognosis of human umbilical cord mesenchymal stem cells in patients with chronic hepatitis B‐induced decompensated liver cirrhosis

Fang, Xueqing; Liu, Liwei; Dong, Jing; Zhang, Junfei; Song, Haiyan; Song, Youliang; Huang, Yizhe; Cui, Xiaoling; Lin, Jinxiu; Chen, Congxin; Liu, Bo; Chen, Zhaolin; Pan, Jingjing; Chen, Xi

doi:10.1111/jgh.14081

Cited by 40 publications

(42 citation statements)

References 31 publications

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“…Pugh scores from 4 to 36 weeks after treatment and decreased the mortality rate during the follow-up period, they demonstrated no remarkable differences in the incidence of developing liver failure in MSC group and control group 80. On the other hand, it has been shown that administration of MSCs reduces jaundice symptoms and decreases serum levels of aminotransferases and bilirubin in patients with HCV-induced liver fibrosis 2.…”

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confidence: 96%

Strategies to improve the efficiency of mesenchymal stem cell transplantation for reversal of liver fibrosis

Zhao

Duan

et al. 2019

J Cellular Molecular Medi

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End‐stage liver fibrosis frequently progresses to portal vein thrombosis, formation of oesophageal varices, hepatic encephalopathy, ascites, hepatocellular carcinoma and liver failure. Mesenchymal stem cells (MSCs), when transplanted in vivo, migrate into fibrogenic livers and then differentiate into hepatocyte‐like cells or fuse with hepatocytes to protect liver function. Moreover, they can produce various growth factors and cytokines with anti‐inflammatory effects to reverse the fibrotic state of the liver. In addition, only a small number of MSCs migrate to the injured tissue after cell transplantation; consequently, multiple studies have investigated effective strategies to improve the survival rate and activity of MSCs for the treatment of liver fibrosis. In this review, we intend to arrange and analyse the current evidence related to MSC transplantation in liver fibrosis, to summarize the detailed mechanisms of MSC transplantation for the reversal of liver fibrosis and to discuss new strategies for this treatment. Finally, and most importantly, we will identify the current problems with MSC‐based therapies to repair liver fibrosis that must be addressed in order to develop safer and more effective routes for MSC transplantation. In this way, it will soon be possible to significantly improve the therapeutic effects of MSC transplantation for liver regeneration, as well as enhance the quality of life and prolong the survival time of patients with liver fibrosis.

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mentioning

confidence: 96%

Strategies to improve the efficiency of mesenchymal stem cell transplantation for reversal of liver fibrosis

Zhao

Duan

et al. 2019

J Cellular Molecular Medi

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“…It is worth mentioning that some in ammatory factors including IL-6, TNF-α, and CD8 + T cells, which are induced by bacteria and endotoxins (lipopolysaccharide, LPS) from gut, are signi cantly decreased after the BMSCs application in liver failure [30]. Previous studies have indicated that gut plays a signi cant role in endotoxemia based on liver failure.…”

Section: Discussionmentioning

confidence: 99%

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

Jiang¹,

Xia²,

Yang³

et al. 2020

Preprint

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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.

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“…Moreover, MSCs also increased the levels of CD4+ T cells and Tregs but decreased the levels of CD8+ T cells and B cells. Although MSCs did not attenuate the development of liver failure compared with standard treatments, they remarkably decreased the level of aspartate aminotransferase and improved the levels of albumin and total bilirubin and the prothrombin time [12]. When added to entecavir treatment, autologous MSCs further improved liver function in hepatitis B virus-induced liver cirrhosis patients.…”

Section: Immunoregulation Of Mscs In Treating Nafld and Liver Fibrosismentioning

confidence: 91%

“…They are able to give rise to mesodermal lineages including adipocytes, osteocytes and chondrocytes [10]. Moreover, transplanted MSCs take part in liver regeneration by migrating toward injured tissues, participating in hepatocyte differentiation and paracrine mechanisms and having immunomodulatory properties [11][12][13]. In vitro culture with specific growth factors promoted the hepatogenic differentiation of MSCs into hepatocyte-like cells (HLCs) with liver-specific morphology and liver functions, including abilities to uptake low-density lipoprotein and indocyanine green, secrete albumin and urea, and store glycogen and the cells also had cytochrome P450 activity [14].…”

Section: Ivyspringmentioning

confidence: 99%

Mesenchymal stromal cells promote liver regeneration through regulation of immune cells

Wang

2020

Int. J. Biol. Sci.

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The liver is sensitive to pathogen-induced acute or chronic liver injury, and liver transplantation (LT) is the only effective strategy for end-stage liver diseases. However, the clinical application is limited by a shortage of liver organs, immunological rejection and high cost. Mesenchymal stromal cell (MSC)-based therapy has gradually become a hot topic for promoting liver regeneration and repairing liver injury in various liver diseases, since MSCs are reported to migrate toward injured tissues, undergo hepatogenic differentiation, inhibit inflammatory factor release and enhance the proliferation of liver cells in vivo. MSCs exert immunoregulatory effects through cell-cell contact and the secretion of anti-inflammatory factors to inhibit liver inflammation and promote liver regeneration. In addition, MSCs are reported to effectively inhibit the activation of cells of the innate immune system, including macrophages, natural killer (NK) cells, dendritic cells (DCs), monocytes and other immune cells, and inhibit the activation of cells of the adaptive immune system, including T lymphocytes, B lymphocytes and subsets of T cells or B cells. In the current review, we mainly focus on the potential effects and mechanisms of MSCs in inhibiting the activation of immune cells to attenuate liver injury in models or patients with acute liver failure (ALF), nonalcoholic fatty liver disease (NAFLD), and liver fibrosis and in patients or models after LT. We highlight that MSC transplantation may replace general therapies for eliminating acute or chronic liver injury in the near future.

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A study about immunomodulatory effect and efficacy and prognosis of human umbilical cord mesenchymal stem cells in patients with chronic hepatitis B‐induced decompensated liver cirrhosis

Abstract: This therapeutic method may be an appropriate choice for patients with decompensated liver cirrhosis.

Cited by 40 publications

References 31 publications

Strategies to improve the efficiency of mesenchymal stem cell transplantation for reversal of liver fibrosis

Strategies to improve the efficiency of mesenchymal stem cell transplantation for reversal of liver fibrosis

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

Mesenchymal stromal cells promote liver regeneration through regulation of immune cells

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