Stem Cells as a Treatment for Chronic Liver Disease and Diabetes

Department of Surgical Oncology and Technology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Handbook of experimental pharmacology 02/2007; 180(180):243-62. DOI: 10.1007/978-3-540-68976-8_11
Source: PubMed


Advances in stem cell biology and the discovery of pluripotent stem cells have made the prospect of cell therapy and tissue regeneration a clinical reality. Cell therapies hold great promise to repair, restore, replace or regenerate affected organs and may perform better than any pharmacological or mechanical device. There is an accumulating body of evidence supporting the contribution of adult stem cells, in particular those of bone marrow origin, to liver and pancreatic islet cell regeneration. In this review, we will focus on the cell therapy for the diseased liver and pancreas by adult haematopoietic stem cells, as well as their possible contribution and application to tissue regeneration. Furthermore, recent progress in the generation, culture and targeted differentiation of human haematopoietic stem cells to hepatic and pancreatic lineages will be discussed. We will also explore the possibility that stem cell technology may lead to the development of clinical modalities for human liver disease and diabetes.

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Available from: Nagy Habib, Apr 15, 2014
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    • "So, from this aspect, the present study evaluated the effect of MSCs and a novel water soluble curcumin derivative (NCD) on notch signaling in hepatoma cell line (HepG2 cells). Advances in stem cell biology have made the prospect of cell therapy and tissue regeneration a clinical reality [33]. Stem cells and tumor cells share similar signaling pathways that regulate self-renewal and differentiation, including the Wnt, Notch, Shh, and BMP pathways that determine the diverse developmental fates of cells [24]. "
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    ABSTRACT: This study was conducted to evaluate the effect of mesenchymal stem cells (MSCs) and a novel curcumin derivative (NCD) on HepG2 cells (hepatoma cell line) and to investigate their effect on Notch1 signaling pathway target genes. HepG2 cells were divided into HepG2 control group, HepG2 cells treated with MSC conditioned medium (MSCs CM), HepG2 cells treated with a NCD, HepG2 cells treated with MSCs CM and NCD, and HepG2 cells treated with MSCs CM (CM of MSCs pretreated with a NCD). Expression of Notch1, Hes1, VEGF, and cyclin D1 was assessed by real-time, reverse transcription-polymerase chain reaction (RT-PCR) in HepG2 cells. In addition, HepG2 proliferation assay was performed in all groups. Notch1 and its target genes (Hes1 and cyclin D1) were downregulated in all treated groups with more suppressive effect in the groups treated with both MSCs and NCD. Also, treated HepG2 cells showed significant decrease in cell proliferation rate. These data suggest that modulation of Notch1 signaling pathway by MSCs and/or NCD can be considered as a therapeutic target in HCC.
    Full-text · Article · Aug 2013
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    • "Advances in stem cell biology have made the prospect of cell therapy and tissue regeneration a clinical reality[7]. In this rapidly expanding field of cell based therapy, more attention has been paid to the relationship between stem cells and tumor cells. "
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    ABSTRACT: The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis. Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl(4), rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups. Histopathological examination of liver tissue from animals which received DENA-CCl(4) only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated β-catenin, proliferating cell nuclear antigen (PCNA), cyclin D and survivin genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect. Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.
    Full-text · Article · May 2011 · Journal of Experimental & Clinical Cancer Research
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    • "For example, recent published data has used human CD34+ adult bone marrow stem cells for the treatment of chronic liver disease and has shown an impressive outcome [Gordon et al., 2006;Levicar et al., 2008]. Haematopoietic stem cells have also being used in many clinical (Phase I) trails in the treatment of ischaemic heart disease, diabetes and other neurodegenerative diseases with an impressive preliminary outcome [Balsam and Robbins, 2005;Dimarakis et al., 2005;Levicar et al., 2007]. However, long-term outcome clinical data has still to be documented and carefully evaluated. "

    Full-text · Chapter · Mar 2011
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