scholarly journals Applications of Mesenchymal Stem Cells in Liver Fibrosis: Novel Strategies, Mechanisms, and Clinical Practice

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Mengmei Zhu ◽  
Tianzhen Hua ◽  
Tao Ouyang ◽  
Huofu Qian ◽  
Bing Yu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Clinical Practice ◽  
Liver Fibrosis ◽  
Early Stage ◽  
Research Progress ◽  
Nutritional Factors ◽  
Hepatocyte Regeneration ◽  
Complete Reversal ◽  
Promising Treatment

Liver fibrosis is a common result of most chronic liver diseases, and advanced fibrosis often leads to cirrhosis. Currently, there is no effective treatment for liver cirrhosis except liver transplantation. Therefore, it is important to carry out antifibrosis treatment to reverse liver damage in the early stage of liver fibrosis. Mesenchymal stem cells (MSCs) are the most widely used stem cells in the field of regenerative medicine. The preclinical and clinical research results of MSCs in the treatment of liver fibrosis and cirrhosis show that MSC administration is a promising treatment for liver fibrosis and cirrhosis. MSCs reverse liver fibrosis and increase liver function mainly through differentiation into hepatocytes, immune regulation, secretion of cytokines and other nutritional factors, reduction of hepatocyte apoptosis, and promotion of hepatocyte regeneration. Recently, many studies provided a variety of new methods and strategies to improve the effect of MSCs in the treatment of liver fibrosis. In this review, we summarized the current effective methods and strategies and their potential mechanisms of MSCs in the treatment of liver fibrosis, as well as the current research progress in clinical practice. We expect to achieve complete reversal of liver injury with MSC-based therapy in the future.

scholarly journals Therapeutic Effects of CXCL9-overexpressing Human Umbilical Cord Mesenchymal Stem Cells on Liver Fibrosis in Rats

2021 ◽  
Author(s):  
Yang Li ◽  
Xueshuai Ye ◽  
Xueqian Zhang ◽  
Ziqi Cai ◽  
Li Shen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Umbilical Cord ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Promising Treatment ◽  
The Impact ◽  
Chemotactic Ability ◽  
Injured Liver

Abstract Background: Umbilical cord mesenchymal stem cells (UC-MSCs) transplantation have become a promising treatment for liver fibrosis. However, UC-MSCs have limited anti-fibrosis ability, and their homing ability of UC-MSCs to the injured liver sites appears to be poor. In this study, we aimed to determining if overexpression of CXCL9 could have the synergistic anti-fibrosis effect with UC-MSCs, and whether it can promote the homing ability of UC-MSCs.Methods: Overexpression of CXCL9 in UC-MSCs (CXCL9-UC-MSCs) was attained by transfection of naive UC-MSCs with the lenti-CXCL9-mCherry. The impact of transplanted CXCL9-UC-MSCs on both repairing of liver fibrosis and homing was evaluated and compared with lenti-mCherry empty vector transfected UC-MSCs (control UC-MSCs).Results: After puromycin screening, UC-MSCs could stably express CXCL9 without affecting the stem and differentiation ability of UC-MSCs. In addition, biochemical analysis showed that the liver function of CXCL9-UC-MSCs was significantly increased in comparison with that of control UC-MSCs (P < 0.05). Futhermore, histopathology after 4 weeks of cell therapy demonstrated that the content of collagen fibers decreased obviously, the pseudo-lobules almost disappeared, and the morphology of hepatic lobules was basically normal. Frozen sections were performed 24 hours and 4 weeks after the cell injection. It can be seen that the fluorescence expression of the CXCL9-UC-MSCs group was significantly higher than that of the control UC-MSCs group, which proved that CXCL9-UC-MSCs have a stronger chemotactic ability, and can stay longer than control UC-MSCs in the injured liver.Conclusion: Overexpression of CXCL9 improves the efficacy of UC-MSC therapy for liver fibrosis repair, thereby promoting the homing and staying of UC-MSCs to injured hepatic sites in a rat model of liver fibrosis.

scholarly journals Research progress of the application of mesenchymal stem cells in chronic inflammatory systemic diseases

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Fangfang Huang ◽  
Erick Thokerunga ◽  
Fajian He ◽  
Xinyu Zhu ◽  
Zi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Research Progress ◽  
Systemic Diseases ◽  
Mesenchymal Stem Cell Transplantation ◽  
Promising Treatment ◽  
Long Course ◽  
Immune Imbalance

AbstractChronic inflammatory systemic diseases are the result of the body's immune imbalance, with a long course and recurring episodes. Immunosuppressants are the main treatment, but not all patients respond well to it. Being capable of both self-renewal and differentiation into multiple tissue cells and low immunogenicity, mesenchymal stem cell is a promising treatment for chronic inflammatory systemic diseases. In this article, we describe the research progress and clinical application of mesenchymal stem cells in chronic inflammatory systemic diseases and look for influencing factors and biomarkers that can predict the outcome of patient with mesenchymal stem cell transplantation.

scholarly journals EBF1 is expressed in pericytes and contributes to pericyte cell commitment

2021 ◽  
Author(s):  
Francesca Pagani ◽  
Elisa Tratta ◽  
Patrizia Dell’Era ◽  
Manuela Cominelli ◽  
Pietro Luigi Poliani
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
B Cell ◽  
Cell Fate ◽  
Early Stage ◽  
Cell Lineage ◽  
Cell Maturation ◽  
Cell Commitment

AbstractEarly B-cell factor-1 (EBF1) is a transcription factor with an important role in cell lineage specification and commitment during the early stage of cell maturation. Originally described during B-cell maturation, EBF1 was subsequently identified as a crucial molecule for proper cell fate commitment of mesenchymal stem cells into adipocytes, osteoblasts and muscle cells. In vessels, EBF1 expression and function have never been documented. Our data indicate that EBF1 is highly expressed in peri-endothelial cells in both tumor vessels and in physiological conditions. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS) analysis suggest that EBF1-expressing peri-endothelial cells represent bona fide pericytes and selectively express well-recognized markers employed in the identification of the pericyte phenotype (SMA, PDGFRβ, CD146, NG2). This observation was also confirmed in vitro in human placenta-derived pericytes and in human brain vascular pericytes (HBVP). Of note, in accord with the key role of EBF1 in the cell lineage commitment of mesenchymal stem cells, EBF1-silenced HBVP cells showed a significant reduction in PDGFRβ and CD146, but not CD90, a marker mostly associated with a prominent mesenchymal phenotype. Moreover, the expression levels of VEGF, angiopoietin-1, NG2 and TGF-β, cytokines produced by pericytes during angiogenesis and linked to their differentiation and activation, were also significantly reduced. Overall, the data suggest a functional role of EBF1 in the cell fate commitment toward the pericyte phenotype.

scholarly journals Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice

2018 ◽  
Vol 8 (3) ◽  
pp. 271-284 ◽  
Author(s):  
Yusuke Watanabe ◽  
Atsunori Tsuchiya ◽  
Satoshi Seino ◽  
Yuzo Kawata ◽  
Yuichi Kojima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis

scholarly journals Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 379
Author(s):  
Rabia Ikram ◽  
Shamsul Azlin Ahmad Shamsuddin ◽  
Badrul Mohamed Jan ◽  
Muhammad Abdul Qadir ◽  
George Kenanakis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Biological Properties ◽  
Research Progress ◽  
Differentiation Potential ◽  
Graphene Derivatives ◽  
Potential Applicability

Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

scholarly journals Human placental mesenchymal stem cells ameliorate liver fibrosis in mice by upregulation of Caveolin1 in hepatic stellate cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yunqi Yao ◽  
Zhemin Xia ◽  
Fuyi Cheng ◽  
Qingyuan Jang ◽  
Jiao He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Therapeutic Effect ◽  
Hepatic Stellate Cells ◽  
Time Window ◽  
Stellate Cells ◽  
Therapeutic Benefits ◽  
Placental Mesenchymal Stem Cells

Abstract Background Liver fibrosis (LF) is a common pathological process characterized by the activation of hepatic stellate cells (HSCs) and accumulation of extracellular matrix. Severe LF causes cirrhosis and even liver failure, a major cause of morbidity and mortality worldwide. Transplantation of human placental mesenchymal stem cells (hPMSCs) has been considered as an alternative therapy. However, the underlying mechanisms and the appropriate time window for hPMSC transplantation are not well understood. Methods We established mouse models of CCl4-injured LF and administered hPMSCs at different stages of LF once a week for 2 weeks. The therapeutic effect of hPMSCs on LF was investigated, according to histopathological and blood biochemical analyses. In vitro, the effect of hPMSCs and the secretomes of hPMSCs on the inhibition of activated HSCs was assessed. RNA sequencing (RNA-seq) analysis, real-time PCR array, and western blot were performed to explore possible signaling pathways involved in treatment of LF with hPMSCs. Results hPMSC treatment notably alleviates experimental hepatic fibrosis, restores liver function, and inhibits inflammation. Furthermore, the therapeutic effect of hPMSCs against mild-to-moderate LF was significantly greater than against severe LF. In vitro, we observed that the hPMSCs as well as the secretomes of hPMSCs were able to decrease the activation of HSCs. Mechanistic dissection studies showed that hPMSC treatment downregulated the expression of fibrosis-related genes, and this was accompanied by the upregulation of Caveolin-1 (Cav1) (p < 0.001). This suggested that the amelioration of LF occurred partly due to the restoration of Cav1 expression in activated HSCs. Upregulation of Cav1 can inhibit the TGF-β/Smad signaling pathway, mainly by reducing Smad2 phosphorylation, resulting in the inhibition of activated HSCs, whereas this effect could be abated if Cav1 was silenced in advance by siRNAs. Conclusions Our findings suggest that hPMSCs could provide multifaceted therapeutic benefits for the treatment of LF, and the TGF-β/Cav1 pathway might act as a therapeutic target for hPMSCs in the treatment of LF.

scholarly journals The Art of Mesenchymal Stem Cells in Liver Fibrosis Management

2021 ◽  
Vol 3 (2) ◽  
pp. 15-24
Author(s):  
Farid Amansyah ◽  
Dito Anurogo
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Tissue Damage ◽  
Fundamental Concept ◽  
Scientific Review ◽  
Safety And Efficacy ◽  
Experimental Animals

Liver fibrogenesisis chronic tissue damage characterized by an extracellular ac-cumulation of fibrillar matrix associated with continuous degradation and remod-elling. This scientific review describes current concepts on the pathophysiology of liver fibrosis, inflammation asa fundamental concept of liver fibrosis, mechanistic concepts of liver fibrosis, the role of mesenchymal stem cells (MSC) in liver injury, the functional effects of MSC secretome, the advantages of secretome ther-apy, and the latest research developments on MSC. The role of MSCs has been proven in many liver fibrosis studies involving experimental animals. However, it still requires further research for safety and efficacy aspects.

scholarly journals Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

2021 ◽  
Vol 40 (1) ◽  
pp. 29
Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Difference ◽  
T1 And T2

Introduction<br />Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase.<br /><br />Methods<br />In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. <br /><br />Results<br />The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p&lt;0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.<br /><br />Conclusion<br />MSCs can suppress TGF levels in liver fibrosis induced rats.

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