Search results for "Liver regeneration"

Role of caspase-8 in hepatocyte response to infection and injury in mice.

2007

Caspase-8 has been implicated in signaling for apoptotic cell death and for certain nonapoptotic functions. However, knowledge of actual physiological or pathophysiological processes to which this enzyme contributes is lacking. Using a mouse model and employing the conditional knockout approach to delete the caspase-8 gene specifically in the liver, we found that caspase-8 deficiency in hepatocytes facilitates infection of the liver by Listeria monocytogenes, attenuates the hepatocyte proliferation wave during the first 48 hours after partial hepatectomy and, depending on the genetic background of the mice, prompts a chronic inflammatory response to the hepatectomy, as a result of which the…

Intracellular accumulation of incompletely processed transforming growth factor-alpha polypeptides in ground glass hepatocytes of chronic hepatitis B…

1996

Abstract Background: Transforming growth factor-alpha is an intracellularly processed and secreted polypeptide that induces a proliferative response in epithelial target cells and represents a potential regulatory factor in embryonic development, liver regeneration, and also hepatocarcinogenesis. We have observed focal transforming growth factor-alpha expression in liver tissues with chronic hepatitis B virus infection. Methods: To further elucidate the nature of this focal transforming growth factor-alpha accumulation were have analyzed overall 23 different liver tissues with chronic hepatitis B virus and hepatitis C virus infection as well as normal liver tissues by immunohistology, ELISA…

Liver regeneration induced by a designer human IL‐6/ sIL‐6R fusion protein reverses severe hepatocellular injury

2000

The cytokine IL-6 plays a significant role in liver regeneration in conjunction with additional growth factors (HGF, TNF-α, and TGF-α). Many IL-6 effects depend on a naturally occurring soluble IL-6 receptor (sIL-6R). Here, the chimeric protein hyper-IL-6, constructed from the human IL-6 protein fused to a truncated form of its receptor, was found to have superagonistic IL-6 properties, and as such, enhanced liver cell regeneration. Hyper-IL-6 reversed the state of hepatotoxicity and enhanced the survival rates of rats suffering from fulminant hepatic failure after D-galactosamine administration. The hyper-IL-6 protein has a significant potential for use in the treatment of severe human liv…

Recent patents and advances in hepatocyte-like cells differentiation by mesenchymal stem cells

2013

Chronic liver diseases constitute one of the main causes of death in western countries. Orthotopic liver transplantation still remains the final therapeutic approach to these diseases, but alternative therapeutic strategies are actively researched. Hepatocyte transplantation is considered a promising approach, even if this technique presents many limitations. These factors boosted the research for alternative cell sources to derive functional hepatocytes. In the last years, research on basic biology and differentiative ability of adult, embryonic and perinatal stem cells has constantly increased. The term "perinatal" indicates stem cell populations derived from foetal sources such as placen…

Targeting PCSK9 for therapeutic gains: Have we addressed all the concerns?

2016

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) regulates the expression of low-density lipoprotein (LDL)-receptors, through reducing their recycling by binding to the receptor along with LDL and targeting it for lysosomal destruction. PCSK9 also enhances the degradation of very-low-density-lipoprotein receptor (VLDLR) and lipoprotein receptor-related protein 1 (LRP-1) in a LDL-receptor independent manner. This role in lipid homeostasis presents PCSK9 as an attractive target for the therapeutic management of familial hypercholesterolemia as well as other refractory dyslipidaemias. However, PCSK9 mediates multifarious functions independent of its role in lipid homeostasis, which can be…

Improving the Techniques for Human Hepatocyte Transplantation: Report from a Consensus Meeting in London

2012

On September 6 and 7, 2009 a meeting was held in London to identify and discuss what are perceived to be current roadblocks to effective hepatocyte transplantation as it is currently practiced in the clinics and, where possible, to offer suggestions to overcome the blocks and improve the outcomes for this cellular therapy. Present were representatives of most of the active clinical hepatocyte transplant programs along with other scientists who have contributed substantial basic research to this field. Over the 2-day sessions based on the experience of the participants, numerous roadblocks or challenges were identified, including the source of cells for the transplants and problems with tra…

Physiological and practical considerations on liver regeneration after liver transplantion

2019

La regeneración hepática ha sido uno de los procesos más estudiados en la medicina al ser el hígado un órgano altamente importante y complejo del organismo, asiento de múltiples enfermedades y expuesto por su ubicación anatómica a los traumatismos. El trasplante hepático se ha convertido en uno de los procedimientos más frecuentes en la trasplantología de órganos, por lo que el conocimiento de los aspectos básicos de esta técnica terapéutica y el estudio de los mecanismos histológicos y fisiológicos vinculados con la regeneración hepática, es fundamental para lograr un resultado satisfactorio. Se realizó un estudio exploratorio de la bibliografía vinculada con el tema, con el objetivo de ex…

2020

We previously demonstrated that clinical administration of mobilized CD133+ bone marrow stem cells (BMSC) accelerates hepatic regeneration. Here, we investigated the potential of platelets to modulate CD133+BMSC homing to hepatic endothelial cells and sequestration to warm ischemic livers. Modulatory effects of platelets on the adhesion of CD133+BMSC to human and mouse liver-sinusoidal- and micro- endothelial cells (EC) respectively were evaluated in in vitro co-culture systems. CD133+BMSC adhesion to all types of EC were increased in the presence of platelets under shear stress. This platelet effect was mostly diminished by antagonization of P-selectin and its ligand P-Selectin-Glyco-Ligan…

Management of liver failure: from transplantation to cell-based therapy

2011

The severe shortage of deceased donor organs has driven a search for alternative methods of treating liver failure. In this context, cell-based regenerative medicine is emerging as a promising interdisciplinary field of tissue repair and restoration, able to contribute to improving health in a minimally invasive fashion. Several cell types have allowed long-term survival in experimental models of liver injury, but their therapeutic potential in humans should be regarded with deep caution, because few clinical trials are currently available and the number of patients enrolled so far is too small to assess benefits versus risks. This review summarizes the current literature on the physiologi…

p38 MAPK: A dual role in hepatocyte proliferation through reactive oxygen species

2013

p38 MAPKs are important mediators of signal transduction that respond to a wide range of extracellular stressors such as UV radiation, osmotic shock, hypoxia, pro-inflammatory cytokines, and oxidative stress. The most abundant family member is p38α, which helps to couple cell proliferation and growth in response to certain damaging stimuli. In fact, increased proliferation and impaired differentiation are hallmarks of p38α-deficient cells. It has been reported that reactive oxygen species (ROS) play a critical role in cytokine-induced p38α activation. Under physiological conditions, p38α can function as a mediator of ROS signaling and either activate or suppress cell cycle progression depen…