<i>In vivo</i> hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

Zhang, Guo-zun; Sun, Hui-Cong; Zheng, Libo; Guo, Jinbo; Zhang, Xiaolan

doi:10.3748/wjg.v23.i46.8152

Cited by 57 publications

(49 citation statements)

References 23 publications

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“…It is crucial to mention that the recovery group in our study did not show any amelioration of fibrogenesis or studied parameters after 6 weeks of recovery and our results are in accordance with previous studies [ 11 , 43 , 47 , 63 – 66 ]…”

Section: Discussionsupporting

confidence: 93%

“…Upon BM-MSCs treatment, the mRNA levels of the unique hepatocyte marker Alb increased, while the Afp mRNA level decreased in a time dependent manner and these results agree with a previous study that correlated these changes in expression to the differentiation of BM-MSCs into hepatocyte-like cells and normalization of Alb could possibly need more time [ 47 ].…”

Section: Discussionsupporting

confidence: 90%

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Bone marrow derived-mesenchymal stem cells downregulate IL17A dependent IL6/STAT3 signaling pathway in CCl4-induced rat liver fibrosis

et al. 2018

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Therapeutic potential of bone marrow–derived mesenchymal stem cells (BM-MSCs) has been reported in several animal models of liver fibrosis. Interleukin (IL) 17A, IL6 and Stat3 have been described to play crucial roles in chronic liver injury. However, the modulatory effect of MSCs on these markers was controversial in different diseases. BM-MSCs might activate the IL6/STAT3 signaling pathway and promote cell invasion in hepatocellular carcinoma, but the immunomodulatory role of BM-MSCs on IL17A/IL6/STAT3 was not fully elucidated in liver fibrosis. In the present study, we evaluated the capacity of the BM-MSCs in the modulation of cytokines milieu and signal transducers, based on unique inflammatory genes Il17a and Il17f and their receptors Il17rc and their effect on the IL6/STAT3 pathway in CCl4-induced liver fibrosis in rats. A single dose of BM-MSCs was administered to the group with induced liver fibrosis, and the genes and proteins of interest were evaluated along six weeks after treatment. Our results showed a significant downregulation of Il17a, Il17ra, il17f and Il17rc genes. In accordance, BM-MSCs administration declined IL17, IL2 and IL6 serum proteins and downregulated IL17A and IL17RA proteins in liver tissue. Interestingly, BM-MSCs downregulated both Stat3 mRNA expression and p-STAT3, while Stat5a gene was downregulated and p-STAT5 protein was elevated. Also P-SMAD3 and TGFβR2 proteins were downregulated in response to BM-MSCs treatment. Collectively, we suggest that BM-MSCs might play an immunomodulatory role in the treatment of liver fibrosis through downregulation of IL17A affecting IL6/STAT3 signaling pathway.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Bone marrow derived-mesenchymal stem cells downregulate IL17A dependent IL6/STAT3 signaling pathway in CCl4-induced rat liver fibrosis

et al. 2018

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“…In addition, ascites in patients with decompensated liver cirrhosis could be improved by UCMSCs (6). In a CCl4-induced rat liver brosis model (23), UCMSCs could differentiate into functional hepatocytes that improved both biochemical and histopathologic changes. In addition, secretomes from UCMSCs also reduced the liver expression of multiple brotic factors, collagens, metalloproteinases, TGFβ, and smad proteins in the TGFβ signaling pathway (24).…”

Section: Discussionmentioning

confidence: 99%

Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV-related liver failure and liver cirrhosis

Jia

Shu

Yang

et al. 2020

Preprint

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Background: This study aimed to investigate the therapeutic effect of umbilical cord mesenchymal stem cells (UCMSCs) on HBV-related liver failure and liver cirrhosis and to compare the different efficacies of UCMSCs after different treatment courses. Methods: This was an observational study that retrospectively considered a three-year period during which 513 patients who received stem cell infusion met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University. Eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the times of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and group D received less than 4 weeks. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and MELD scores were recorded and compared among different groups. Results: A total of 64 patients met the criteria of liver failure, and 59 patients met the criteria of liver cirrhosis. After UCMSC treatments, the levels of ALT, AST, and TBIL at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the PTA and MELD scores only gradually improved in the liver failure group. Four weeks after UCMSC treatment, patients with prolonged treatment with UCMSCs had higher TBIL decline levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there was no statistically significant difference in the levels of change for ALT, AST, TBIL, PTA value and the MELD score between patients with liver failure with prolonged treatment with UCMSCs and patients with liver cirrhosis with prolonged treatment with UCMSCs at all observation weeks. However, the median decline and cumulative decline in the TBIL level of patients with liver failure with a standard 4-week treatment course were higher than those of patients with liver cirrhosis with a standard 4-week treatment course. Conclusion: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.

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“…& MSC affect the phenotype of M1 macrophages and promote their change into M2 [175]. & Mesenchymal cells isolated from the postnatal tissues reduce the cytokine storm phenomenon during acute and chronic liver damage, thus reducing the cell apoptosis and necrotic areas [133,142,157,158,176,177]. Acute injurysurgical BDL Decreased: fibronectin deposition, areas occupied by myofibroblasts, number of cells positive for S100A4, TGFβ pathway activation, αvβ6 integrin expression.…”

Section: Preclinical Studies Conducted With Mesenchymal Stem Cellsmentioning

confidence: 99%

Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration

Michalik

Gładyś

Czekaj

2020

Stem Cell Rev and Rep

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Toxic, viral and surgical injuries can pose medical indications for liver transplantation. The number of patients waiting for a liver transplant still increases, but the number of organ donors is insufficient. Hepatocyte transplantation was suggested as a promising alternative to liver transplantation, however, this method has some significant limitations. Currently, afterbirth tissues seem to be an interesting source of cells for the regenerative medicine, because of their unique biological and immunological properties. It has been proven in experimental animal models, that the native stem cells, and to a greater extent, hepatocyte-like cells derived from them and transplanted, can accelerate regenerative processes and restore organ functioning. The effective protocol for obtaining functional mature hepatocytes in vitro is still not defined, but some studies resulted in obtaining functionally active hepatocyte-like cells. In this review, we focused on human stem cells isolated from placenta and umbilical cord, as potent precursors of hepatocyte-like cells for regenerative medicine. We summarized the results of preclinical and clinical studies dealing with the introduction of epithelial and mesenchymal stem cells of the afterbirth origin to the liver failure therapy. It was concluded that the use of native afterbirth epithelial and mesenchymal cells in the treatment of liver failure could support liver function and regeneration. This effect would be enhanced by the use of hepatocyte-like cells obtained from placental and/or umbilical stem cells.

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In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

Cited by 57 publications

References 23 publications

Bone marrow derived-mesenchymal stem cells downregulate IL17A dependent IL6/STAT3 signaling pathway in CCl4-induced rat liver fibrosis

Bone marrow derived-mesenchymal stem cells downregulate IL17A dependent IL6/STAT3 signaling pathway in CCl4-induced rat liver fibrosis

Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV-related liver failure and liver cirrhosis

Differentiation of Cells Isolated from Afterbirth Tissues into Hepatocyte-Like Cells and Their Potential Clinical Application in Liver Regeneration

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