Use of Stem Cells to Block the Activation of Hepatic Stellate Cells in Diseased Liver

2014 ◽  
pp. 221-232 ◽  
Author(s):  
Syamantak Majumder ◽  
Palanivel Gajalakshmi ◽  
Suvro Chatterjee
Keyword(s):  
Stem Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Diseased Liver

Inhibition of hepatic stellate cells proliferation by mesenchymal stem cells and the possible mechanisms

2009 ◽  
Vol 39 (12) ◽  
pp. 1219-1228 ◽  
Author(s):  
Jing Wang ◽  
Chunjing Bian ◽  
Lianming Liao ◽  
Yashu Zhu ◽  
Jing Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells

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 Human Menstrual Blood-Derived Stem Cells Ameliorate Liver Fibrosis in Mice by Targeting Hepatic Stellate Cells via Paracrine Mediators

2016 ◽  
Vol 6 (1) ◽  
pp. 272-284 ◽  
Author(s):  
Lijun Chen ◽  
Chunfeng Zhang ◽  
Lu Chen ◽  
Xiaojun Wang ◽  
Bingyu Xiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Menstrual Blood

scholarly journals Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells

2007 ◽  
Vol 363 (2) ◽  
pp. 247-252 ◽  
Author(s):  
Biju Parekkadan ◽  
Daan van Poll ◽  
Zaki Megeed ◽  
Naoya Kobayashi ◽  
Arno W. Tilles ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Activated Hepatic Stellate Cells

Human bone marrow mesenchymal stem cells suppress the proliferation of hepatic stellate cells by inhibiting the ubiquitination of p27

2017 ◽  
Vol 95 (6) ◽  
pp. 628-633 ◽  
Author(s):  
Liang Wang ◽  
Guang Bai ◽  
Fei Chen
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cell Cycle Arrest ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Cycle Arrest ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) have considerable therapeutic potential for the treatment of end-stage liver disease. Previous studies have demonstrated that BMSCs secrete growth factors and cytokines that inactivate hepatic stellate cells (HSCs), which inhibited the progression of hepatic fibrosis. The aim of this study was to determine the mechanism by which BMSCs suppress the function of HSCs in fibrosis. Our results showed that co-culture of BMSCs and HSCs induced cell cycle arrest at the G10/G1 phase and cell apoptosis of HSCs, which finally inhibited the cell proliferation of HSCs. Consistent with the cell cycle arrest, co-culture of BMSCs and HSCs increased the abundance of the cell cycle protein p27. Mechanistically, we further uncovered that following the co-culture with BMSCs, the expression level of the E3 ligase S-phase kinase-associated protein 2 (SKP2) that is responsible for the ubiquitination of p27 was decreased, which attenuated the ubiquitination of p27 and increased the stability of p27 in HSCs. Collectively, our results indicated the potential involvement of the SKP2–p27 axis for the inhibitory effect of BSMCs on the cell proliferation of HSCs.

scholarly journals Bone marrow mesenchymal stem cells modulate the expression of RhoA and P27 in hepatic stellate cells

2009 ◽  
Vol 17 (32) ◽  
pp. 3283
Author(s):  
Si-Biao Su ◽  
Hai-Xing Jiang ◽  
Dong-Xu Wang ◽  
Shan-Yu Qin ◽  
Zi-Yu Liang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Marrow Mesenchymal Stem Cells

scholarly journals The Hepatic Stellate Cells (HSTCs) and Adipose-derived Mesenchymal Stem Cells (ASCs) Axis as a Potential Major Driver of Metabolic Syndrome – Novel Concept and Therapeutic Implications

2021 ◽  
Author(s):  
Krzysztof Marycz ◽  
Katarzyna Kornicka-Garbowska ◽  
Larry Galuppo ◽  
Lynda Bourebaba
Keyword(s):  
Metabolic Syndrome ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hepatic Stellate Cells ◽  
Metabolic Diseases ◽  
Stellate Cells ◽  
Therapeutic Implications ◽  
Prevention And Treatment ◽  
Novel Concept ◽  
Molecular Crosstalk

Abstract Herein, we would like to introduce a novel concept for the prevention and treatment of metabolic syndrome, which is based on molecular relationship between liver and adipose tissue. Particularly, we believe, that unravelling the molecular crosstalk between hepatokines and adipokines will allow to better understand the pathophysiology of metabolic diseases and allow to develop novel, effective therapeutic solutions against obesity and metabolic syndrome. Graphical Abstract Inter-organ communication on the level of stem progenitor cells-hepatic stellate cells (HSTCs) and adipose-derived progenitors (ASCs) could represents a key mechanism involved in controlling glucose tolerance as well as insulin sensitivity.

Hematopoietic Origin of Hepatic Stellate Cell.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1679-1679
Author(s):  
Eri Miyata ◽  
Masahiro Masuya ◽  
Fumihiko Ishikawa ◽  
Shuro Yoshida ◽  
Keizo Kato ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Injury ◽  
Hematopoietic Stem Cells ◽  
Hepatic Stellate Cells ◽  
Type I Collagen ◽  
Stellate Cells ◽  
Gradual Transition ◽  
Type I ◽  
Chimeric Mice ◽  
Hematopoietic Stem

Abstract Hepatic stellate cells are believed to play a key role in the development of liver fibrosis. They undergo a gradual transition from a quiescent, fat-storing phenotype to an activated myofibroblast-like phenotype and then produce high amount of extracellular matrix such as collagen by liver injury. They express mesenchymal markers such as vimentin and desmin, or neural/neuroectodermal markers such as glial fibrillary acidic protein (GFAP). Based on the characteristic phenotype, the embryonic origin of stellate cells is thought to be the septum transversum mesenchyme or neural crest. However, their origin in the adult liver is still unknown. Recently, several studies have reported that crude bone marrow (BM) cells can give rise to hepatic stellate cells. However, since adult BM cells are thought to contain hematopoietic stem cells and mesenchymal stem cells, it is important to clarify which type of stem cells is the true source of hepatic stellate cells. We hypothesized that hepatic stellate cells are derived from hematopoietic stem cells. To test this hypothesis, we generated chimeric mice by transplantation of singe enhanced green fluorescent protein (EGFP)-marked hematopoietic stem cells (Lin− Sca-1+ c-kit+ CD34− cells) into lethally irradiated nontransgenic mice and examined the histology of liver tissues obtained from chimeric mice with carbon tetrahydrochloride (CCl4)-induced injury. Following 12 weeks treatment of CCl4, hepatic nodules and bridging fibrosis developed in all livers. We detected EGFP+ cells in the liver and some of them contained intracytoplasmic lipid droplets, which were proved by oil red O staining. Immunohistochemical analysis demonstrated that 60% of EGFP+ cells were negative for leukocyte common antigen (CD45); however, they expressed vimentin, GFAP and ADAMTS-13, which is a circulating zinc metalloproteinase synthesized in hepatic stellate cells. Moreover, nonparenchymal cell populations were isolated from the livers of chimeric mice with CCl4 treatment and were incubated on noncoated glass slides for 3 days. EGFP+ cells were also positive for type I collagen. These phenotypes are consistent with those of hepatic stellate cells. Our findings suggest that hematopoietic stem cells contribute to the generation of hepatic stellate cells upon liver injury.

285 HYPOXIA – INDUCED MIGRATION OF HEPATIC STELLATE CELLS AND BONE MARROW – DERIVED MESENCHYMAL STEM CELLS INVOLVES COMMON REDOX MECHANISMS

2009 ◽  
Vol 50 ◽  
pp. S112 ◽  
Author(s):  
E. Novo ◽  
L. Valfrèdi Bonzo ◽  
C. Busletta ◽  
D. Povero ◽  
C. Paternostro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells
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