Stem Cell Therapy for Liver Disease: Parameters Governing the Success of Using Bone Marrow Mesenchymal Stem Cells

Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei, Taiwan.
Gastroenterology (Impact Factor: 13.93). 06/2008; 134(7):2111-21, 2121.e1-3. DOI: 10.1053/j.gastro.2008.03.015
Source: PubMed

ABSTRACT Liver transplantation is the primary treatment for various end-stage hepatic diseases but is hindered by the lack of donor organs and by complications associated with rejection and immunosuppression. There is increasing evidence to suggest the bone marrow is a transplantable source of hepatic progenitors. We previously reported that multipotent bone marrow-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells with almost 100% induction frequency under defined conditions, suggesting the potential for clinical applications. The aim of this study was to critically analyze the various parameters governing the success of bone marrow-derived mesenchymal stem cell-based therapy for treatment of liver diseases.
Lethal fulminant hepatic failure in nonobese diabetic severe combined immunodeficient mice was induced by carbon tetrachloride gavage. Mesenchymal stem cell-derived hepatocytes and mesenchymal stem cells were then intrasplenically or intravenously transplanted at different doses.
Both mesenchymal stem cell-derived hepatocytes and mesenchymal stem cells, transplanted by either intrasplenic or intravenous route, engrafted recipient liver, differentiated into functional hepatocytes, and rescued liver failure. Intravenous transplantation was more effective in rescuing liver failure than intrasplenic transplantation. Moreover, mesenchymal stem cells were more resistant to reactive oxygen species in vitro, reduced oxidative stress in recipient mice, and accelerated repopulation of hepatocytes after liver damage, suggesting a possible role for paracrine effects.
Bone marrow-derived mesenchymal stem cells can effectively rescue experimental liver failure and contribute to liver regeneration and offer a potentially alternative therapy to organ transplantation for treatment of liver diseases.

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Available from: Vincent W Yang, Jan 03, 2014
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    • "From clinically applied stem cells, mesenchymal stem cells (MSCs) have been described as well-characterized stem cells that can be isolated from adult tissues (Jiang et al., 2002). Positive indications of their applications in various diseases have made them clinically promising (Bang et al., 2005, Garcia-Olmo et al., 2005, Kuo et al., 2008, Le Blanc et al., 2008, Nakamizo et al., 2005, Pisati et al., 2007). Many advantages in their application over the embryonic stem cells has made them potential candidates in regenerative medicine (Thomson et al., 1998). "
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    ABSTRACT: Stem cell therapy in recent years has gained much attention as being the modern therapeutic approach to treat diseases. Mesenchymal stem cells (MSCs) are seen as the most reliable cells applied in therapy over other stem cells because of their versatility. Bone and cartilage diseases (osteo-diseases) are the major target of therapy using MSCs. In this perspective, we have analyzed statistically data available on clinical trials registry databases. We report that MSC therapy for osteo-diseases needs optimization in its standards to achieve acceptable results so that we can apply it in daily routine clinical practice.
    Cell Biology International 05/2014; 38(10). DOI:10.1002/cbin.10293 · 1.64 Impact Factor
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    • "A few studies showed beneficial effects. Using a model of carbon tetrachloride induced acute liver failure in immunodeficient mice Kuo et al. showed that intrasplenically or intravenously transplanted human MSCs engrafted into recipient liver, differentiated into functional hepatocytes, and rescued liver failure (Kuo et al., 2008). Similarly, intravenously injected human MSCs derived from adipose tissue also improved liver functions (i.e. "
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    ABSTRACT: Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been extensively investigated in small animal models to treat both acute and chronic liver injuries. Mechanisms of action are not clearly elucidated but may include their ability to differentiate into hepatocyte-like cells, to reduce inflammation, and to enhance tissue repair at the site of injury. This approach is controversial and evidence in large animals is missing. Side effects of MSC infusion such as the contribution to a fibrotic process have been reported in experimental settings. Nevertheless, MSCs moved quickly from bench to bedside and over 280 clinical trials are registered, of which 28 focus on the treatment of liver diseases. If no severe side-effects were observed so far, long-term benefits remain uncertain. More preclinical data regarding mechanisms of action, long term safety and efficacy are warranted before initiating large scale clinical application. The proposal of this review is to visit the current state of knowledge regarding mechanisms behind the therapeutic effects of MSCs in the treatment of experimental liver diseases, to address questions about efficacy and risk, and to discuss recent clinical advances involving MSC-based therapies.
    Stem Cell Research 08/2013; 11(3):1348-1364. DOI:10.1016/j.scr.2013.08.011 · 3.91 Impact Factor
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    • "Therefore, MSCs possess the main enzymatic machinery to detoxify reactive species and to correct oxidative damage of proteome and genome. Accordingly, it has been shown that MSC transplantation is useful in the treatment of pathologies in which tissue damage is linked to oxidative stress including acute myocardial infarction (Chen et al. 2004), cerebral ischaemia (Kurozumi et al. 2005) and fulminant hepatic failure (Kuo et al. 2008). In these cases, the therapeutic effect observed has been attributed, amongst other mechanisms , to their potential to efficiently scavenge exogenous reactive species once homed into the niche of damaged tissues (Lanza et al. 2009). "
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