Role of mesenchymal stem cells, their derived factors, and extracellular vesicles in liver failure

Wang, Jie; Cen, Panpan; Chen, Jiajia; Fan, Linxiao; Li, Jun; Li, Lanjuan

doi:10.1186/s13287-017-0576-4

Cited by 47 publications

(44 citation statements)

References 46 publications

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“…Mesenchymal stem/stromal cells (MSCs) are heterogeneous populations capable of multipotential differentiation together with hematopoietic supporting and immunosuppressive properties [9][10][11]. MSCs have been wildly used in preclinical and clinical studies for disease remodeling including acute-on-chronic liver failure, diabetes, Crohn's disease, and acquired AA [9,[12][13][14][15][16]. Generally, as the key component in the microenvironment, MSCs serve as a potential supplementary alternative for refractory AA treatment and have exhibited unexceptionably therapeutic effect mainly through transdifferentiation, immunomodulatory activity, autocrine, and paracrine together with providing an ideal niche [17,18].…”

Section: Introductionmentioning

confidence: 99%

Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia

et al. 2020

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Background: Longitudinal studies have verified the pivotal role of mesenchymal stem/stromal cells (MSCs) in the bone marrow microenvironment for hematopoiesis and coordinate contribution to leukemia pathogenesis. However, the precise characteristics and alternation of MSCs during acquired aplastic anemia (AA) remain obscure. Methods: In this study, we originally collected samples from both healthy donors (HD) and AA patients to dissect the hematological changes. To systematically evaluate the biological defects of AA-derived MSCs (AA-MSCs), we analyzed alterations in cellular morphology, immunophenotype, multi-lineage differentiation, cell migration, cellular apoptosis, and chromosome karyocyte, together with the immunosuppressive effect on the activation and differentiation of lymphocytes. With the aid of whole genome sequencing and bioinformatic analysis, we try to compare the differences between AA-MSCs and HD-derived MSCs (HD-MSCs) upon the molecular genetics, especially the immune-associated gene expression pattern. In addition, the efficacy of umbilical cord-derived MSC (UC-MSC) transplantation on AA mice was evaluated by utilizing survivorship curve, histologic sections, and blood cell analyses. Results: In coincidence with the current reports, AA patients showed abnormal subsets of lymphocytes and higher contents of proinflammatory cytokines. Although with similar immunophenotype and chromosome karyotype to HD-MSCs, AA-MSCs showed distinguishable morphology and multiple distinct characteristics including genetic properties. In addition, the immunosuppressive effect on lymphocytes was significantly impaired in AA-MSCs. What is more, the cardinal symptoms of AA mice were largely rescued by systemic transplantation of UC-MSCs. Conclusions: Herein, we systematically investigated the signatures and efficacy of MSCs to dissect the alterations occurred in AA both at the cellular and molecular levels. Different from HD-MSCs, AA-MSCs exhibited multifaceted defects in biological characteristics and alterative molecular genetics in the whole genome. Our findings have provided systematic and overwhelming new evidence for the defects of AA-MSCs, together with effectiveness assessments of UC-MSCs on AA as well.

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Section: Introductionmentioning

confidence: 99%

Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia

et al. 2020

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“…Therefore, hUCMSCs have higher utilization value and can be used for mass production [30]. Many published articles have demonstrated MSCs to be therapeutic in liver failure by secretion of trophic and immunomodulatory factors that support hepatocyte function, promote proliferation, inhibit apoptosis, promote angiogenesis, and reverse liver fibrosis before transdifferentiation [31]. They create a microenvironment for tissue regeneration while restraining life-threating cytokine storms and immunocyte infiltration.…”

Section: Discussionmentioning

confidence: 99%

In a Rat Model of Acute Liver Failure, Icaritin Improved the Therapeutic Effect of Mesenchymal Stem Cells by Activation of the Hepatocyte Growth Factor/c-Met Pathway

Wang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Acute liver failure (ALF) is a serious life-threatening condition. Mesenchymal stem cells (MSCs) may be an effective treatment for this condition and a good alternative to liver transplantation. Icaritin (ICT) is an active ingredient of the genus Epimedium, a traditional Chinese medicine, with the potential to enhance the proliferation of MSCs. The purpose of this study was to explore whether ICT increased the therapeutic effects of MSCs and explore its underlying mechanisms. For in vivo experiments, a rat ALF model was established by intraperitoneal injection of D(+)-galactosamine/ lipopolysaccharide. MSCs cocultured with ICT were used to treat ALF rats and the protective effects assessed as survival rate, levels of serum AST and ALT, and histological changes in liver tissue. For in vitro experiments, MSCs were treated in serum-free culture for 72 h to simulate the disruption of intrahepatic microcirculation. MSCs apoptosis was examined to determine whether ICT rescued impaired MSCs. The role of the hepatocyte growth factor (HGF)/c-Met pathway in MSCs was assessed by constructing genetically modified MSCs overexpressing c-Met and by using the c-Met receptor inhibitor (crizotinib). The results showed that MSCs increased the survival rate of ALF rats and reduced liver damage. MSCs cocultured with ICT exerted a greater therapeutic effect than MSCs alone. Further, the HGF/c-Met pathway played a key role in the antiapoptotic activity of MSCs, which was associated with the optimized efficacy of ICT. In conclusion, this study demonstrated that ICT enhances the therapeutic effect of MSCs in a model of ALF, improving the antiapoptotic potential of MSCs by upregulation of the HGF/c-Met pathway. The combination of stem cell therapy with traditional herbal extracts may improve MSC-based clinical applications.

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“…The molecular mechanisms underlying these beneficial effects are manifold, but are believed to be derived from paracrine factors affecting apoptosis, immune responses, stellate cell activation, angiogenesis, etc. (as reviewed in [76][77][78]). Moreover, as for BM-HSCs and BMMs, fusion of human MSCs with host liver cells has been suggested [79].…”

Section: Undifferentiated Mesenchymal Stromal Cellsmentioning

confidence: 99%

Alternative Cell Sources for Liver Parenchyma Repopulation: Where Do We Stand?

Tricot

Boeck

Verfaillie

2020

Cells

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Acute and chronic liver failure is a highly prevalent medical condition with high morbidity and mortality. Currently, the therapy is orthotopic liver transplantation. However, in some instances, chiefly in the setting of metabolic diseases, transplantation of individual cells, specifically functional hepatocytes, can be an acceptable alternative. The gold standard for this therapy is the use of primary human hepatocytes, isolated from livers that are not suitable for whole organ transplantations. Unfortunately, primary human hepatocytes are scarcely available, which has led to the evaluation of alternative sources of functional hepatocytes. In this review, we will compare the ability of most of these candidate alternative cell sources to engraft and repopulate the liver of preclinical animal models with the repopulation ability found with primary human hepatocytes. We will discuss the current shortcomings of the different cell types, and some of the next steps that we believe need to be taken to create alternative hepatocyte progeny capable of regenerating the failing liver.

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Role of mesenchymal stem cells, their derived factors, and extracellular vesicles in liver failure

Cited by 47 publications

References 46 publications

Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia

Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia

In a Rat Model of Acute Liver Failure, Icaritin Improved the Therapeutic Effect of Mesenchymal Stem Cells by Activation of the Hepatocyte Growth Factor/c-Met Pathway

Alternative Cell Sources for Liver Parenchyma Repopulation: Where Do We Stand?

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