Serum from CCl<sub>4</sub>-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis

Baig, Maria Tayyab; Ali, Gibran; Awan, Sana Javaid; Shehzad, Umara; Mehmood, Azra; Mohsin, Sadia; Khan, Shaheen N.; Riazuddin, Sheikh

doi:10.1080/08977194.2017.1392945

Cited by 11 publications

(11 citation statements)

References 77 publications

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“…Immortalized cells were cultured in Opti-MEM medium supplemented with 10% FBS. In order to determine the HPC population, we compared the corresponding mRNA expression profile of genes encoding (1) HPCs and hepatic specific markers, such as α-fetoprotein ( AFP ), hepatocyte nuclear factor 4 α ( HNF4A ), and alanine aminotransferase ( ALAT ) [21]; (2) HPCs and cholangiocyte-specific markers ( SOX9 ) [22] and epithelial cell adhesion molecule ( EPCAM ) [16]; (3) adipose-derived mesenchymal stem cell (ASCs) markers, such as CD105 and CD90 [23]; as well as an endothelial cell specific marker, platelet and endothelial cell adhesion molecule 1 ( PECAM1 ) [24]. We found that similarly to whole liver tissue, cultured HPCs expressed HNF4A and ALAT.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of the Low Molecular Weight Protein Tyrosine Phosphatase (LMPTP) as a Potential Therapeutic Strategy for Hepatic Progenitor Cells Lipotoxicity—Short Communication

Alicka

Kornicka

Roecken³

et al. 2019

IJMS

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Equine metabolic syndrome (EMS) is a cluster of metabolic disorders, such as obesity, hyperinsulinemia, and hyperleptinemia, as well as insulin resistance (IR). In accordance with the theory linking obesity and IR, excessive accumulation of lipids in insulin-sensitive tissues (lipotoxicity), like liver, alters several cellular functions, including insulin signaling. Therefore, the purpose of the study was to isolate equine hepatic progenitor-like cells (HPCs) and assess whether inhibition of low molecular weight protein tyrosine phosphatase (LMPTP) affects the expression of genes involved in macroautophagy, chaperone-mediated autophagy (CMA), endoplasmic reticulum stress, and mitochondrial dynamics in a palmitate-induced IR model. We demonstrated that LMPTP inhibition significantly enhanced expression of heat shock cognate 70 kDa protein (HSC70), lysosome-associated membrane protein 2 (LAMP2), and parkin (PRKN), all master regulators of selective autophagy. We also observed downregulation of C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and binding immunoglobulin protein encoded by the HSPA gene. Moreover, LMPTP inhibition increased alternative splicing of X-box binding protein 1 (XBP1), suggesting high endonuclease activity of inositol-requiring enzyme 1 alpha (IRE1α). Taken together, our data provide convincing evidence that LMPTP inhibition reverses palmitate-induced insulin resistance and lipotoxicity. In conclusion, this study highlights the role of LMPTP in the regulation of CMA, mitophagy, and ER stress, and provides a new in vitro model for studying HPC lipotoxicity in pre-clinical research.

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Section: Resultsmentioning

confidence: 99%

Inhibition of the Low Molecular Weight Protein Tyrosine Phosphatase (LMPTP) as a Potential Therapeutic Strategy for Hepatic Progenitor Cells Lipotoxicity—Short Communication

Alicka

Kornicka

Roecken³

et al. 2019

IJMS

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“…After incubation with serum from rats with acute CCl 4 injury, ADMSCs demonstrated polygonal morphology and expressed AFP, ALB, and CK8 and other hepatocyte markers. Moreover, ADMSCs preconditioned with serum from rats with acute CCl 4 injury significantly improved liver function and reduced liver fibrosis in CCl 4 -induced liver fibrosis, as demonstrated by higher expression of hepatic and pro-survival markers and improvement in liver structure [110]. Exposure to basic fibroblast growth factor obviously upregulated the proliferation and differentiation of ADMSCs in vitro and enhanced the ability of ADMSCs to suppress the progression of liver fibrosis via elevation of HGF expression, promotion of HSC apoptosis, and enhancement of hepatocyte proliferation [83].…”

Section: Introductionmentioning

confidence: 99%

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

Zhao

2019

Stem Cell Res Ther

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The liver, the largest organ with multiple synthetic and secretory functions in mammals, consists of hepatocytes, cholangiocytes, hepatic stellate cells (HSCs), sinusoidal endothelial cells, Kupffer cells (KCs), and immune cells, among others. Various causative factors, including viral infection, toxins, autoimmune defects, and genetic disorders, can impair liver function and result in chronic liver disease or acute liver failure. Mesenchymal stem cells (MSCs) from various tissues have emerged as a potential candidate for cell transplantation to promote liver regeneration. Adipose-derived MSCs (ADMSCs) with high multi-lineage potential and self-renewal capacity have attracted great attention as a promising means of liver regeneration. The abundance source and minimally invasive procedure required to obtain ADMSCs makes them superior to bone marrow-derived MSCs (BMMSCs). In this review, we comprehensively analyze landmark studies that address the isolation, proliferation, and hepatogenic differentiation of ADMSCs and summarize the therapeutic effects of ADMSCs in animal models of liver diseases. We also discuss key points related to improving the hepatic differentiation of ADMSCs via exposure of the cells to cytokines and growth factors (GFs), extracellular matrix (ECM), and various physical parameters in in vitro culture. The optimization of culturing methods and of the transplantation route will contribute to the further application of ADMSCs in liver regeneration and help improve the survival rate of patients with liver diseases. To this end, ADMSCs provide a potential strategy in the field of liver regeneration for treating acute or chronic liver injury, thus ensuring the availability of ADMSCs for research, trial, and clinical applications in various liver diseases in the future.

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“…Intriguingly, Waterman et al 64 in rats with CCl 4 -induced liver fibrosis. 66 In addition, pre-treatment with inflammatory factors also contributes to improving MSC-based therapeutic effects. Although IFN-γ and a multiple cytokine cocktail consisting of IFN-γ, TGF-β and retinoic acid had no effect on the immunomodulation of MSCs in vivo, they significantly enhanced the capacity of MSCs to inhibit the proliferation of CD4+ T cells and CD8+ T cells and the production of IFN-γ.…”

Section: Pre-treatments With An Altered Microenvironment For Msc-bamentioning

confidence: 99%

Pre‐treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases

Wang

2019

J Cellular Molecular Medi

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Liver diseases caused by viral infection, alcohol abuse and metabolic disorders can progress to end‐stage liver failure, liver cirrhosis and liver cancer, which are a growing cause of death worldwide. Although liver transplantation and hepatocyte transplantation are useful strategies to promote liver regeneration, they are limited by scarce sources of organs and hepatocytes. Mesenchymal stem cells (MSCs) restore liver injury after hepatogenic differentiation and exert immunomodulatory, anti‐inflammatory, antifibrotic, antioxidative stress and antiapoptotic effects on liver cells in vivo. After isolation and culture in vitro, MSCs are faced with nutrient and oxygen deprivation, and external growth factors maintain MSC capacities for further applications. In addition, MSCs are placed in a harsh microenvironment, and anoikis and inflammation after transplantation in vivo significantly decrease their regenerative capacity. Pre‐treatment with chemical agents, hypoxia, an inflammatory microenvironment and gene modification can protect MSCs against injury, and pre‐treated MSCs show improved hepatogenic differentiation, homing capacity, survival and paracrine effects in vitro and in vivo in regard to attenuating liver injury. In this review, we mainly focus on pre‐treatments and the underlying mechanisms for improving the therapeutic effects of MSCs in various liver diseases. Thus, we provide evidence for the development of MSC‐based cell therapy to prevent acute or chronic liver injury. Mesenchymal stem cells have potential as a therapeutic to prolong the survival of patients with end‐stage liver diseases in the near future.

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Serum from CCl₄-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis

Cited by 11 publications

References 77 publications

Inhibition of the Low Molecular Weight Protein Tyrosine Phosphatase (LMPTP) as a Potential Therapeutic Strategy for Hepatic Progenitor Cells Lipotoxicity—Short Communication

Inhibition of the Low Molecular Weight Protein Tyrosine Phosphatase (LMPTP) as a Potential Therapeutic Strategy for Hepatic Progenitor Cells Lipotoxicity—Short Communication

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

Pre‐treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases

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Serum from CCl4-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis

Cited by 11 publications

References 77 publications

Inhibition of the Low Molecular Weight Protein Tyrosine Phosphatase (LMPTP) as a Potential Therapeutic Strategy for Hepatic Progenitor Cells Lipotoxicity—Short Communication

Inhibition of the Low Molecular Weight Protein Tyrosine Phosphatase (LMPTP) as a Potential Therapeutic Strategy for Hepatic Progenitor Cells Lipotoxicity—Short Communication

Current understanding of adipose-derived mesenchymal stem cell-based therapies in liver diseases

Pre‐treatments enhance the therapeutic effects of mesenchymal stem cells in liver diseases

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Serum from CCl₄-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis