https://research.birmingham.ac.uk/portal/files/44770804/Newsome_et_al_Granulocyte_colony_stimulating_factor_Lancet_Gastroenterology.pdf

Granulocyte colony-stimulating factor and autologous CD133-positive stem-cell therapy in liver cirrhosis (REALISTIC): an open-label, randomised, controlled phase 2 trial

Cell Therapy for Advanced Liver Diseases: Repair or Rebuild

Control of homeostasis and rapid response to tissue damage in the liver is orchestrated by crosstalk between resident and infiltrating inflammatory cells. A crucial role for myeloid cells during hepatic injury and repair has emerged where resident Kupffer cells, circulating monocytes, macrophages, dendritic cells and neutrophils control local tissue inflammation and regenerative function to maintain tissue architecture. Studies in humans and rodents have revealed a heterogeneous population of myeloid cells that respond to the local environment by either promoting regeneration or driving the inflammatory processes that can lead to hepatitis, fibrogenesis, and the development of cirrhosis and malignancy. Such plasticity of myeloid cell responses presents unique challenges for therapeutic intervention strategies and a greater understanding of the underlying mechanisms is needed. Here we review the role of myeloid cells in the establishment and progression of liver disease and highlight key pathways that have become the focus for current and future therapeutic strategies.

/pdf/the-role-of-myeloid-derived-cells-in-the-progression-of-3v4zwbxtwd.pdf

The Role of Myeloid-Derived Cells in the Progression of Liver Disease.

Tissue fibrosis, including pulmonary fibrosis, hepatic fibrosis, and cardiac fibrosis, is an important stage in the development of many diseases. It can lead to structural damage and dysfunction and even severe carcinogenesis or death. There is currently no effective method for the treatment of fibrosis. At present, the molecular mechanism of tissue fibrosis has not yet been fully elucidated, but many studies have demonstrated that it is involved in conveying the complex messages between fibroblasts and various cytokines. Sphingosine 1-phosphate (S1P) is a naturally bioactive sphingolipid. S1P and the related signaling pathways are important intracellular metabolic pathways involved in many life activities, including cell proliferation, differentiation, apoptosis, and cellular signal transduction. Increasing evidence suggests that S1P and its signaling pathways play an important role in the development of tissue fibrosis; however, the mechanisms of these effects have not yet been fully elucidated, and even the role of S1P and its signaling pathways are still controversial. This article focuses on the role of S1P and the related signaling pathways in the development of fibrosis of lung, liver, heart, and other tissues, with emphasis on the application of inhibitors of some of molecules in the pathway in clinical treatment of fibrosis diseases.

The Role of S1P and the Related Signaling Pathway in the Development of Tissue Fibrosis.

Sphingolipids are class of metabolically distinct lipids that play structural and signaling functions in all organisms. Sphingolipid metabolism is deregulated during various diseases such as cancer, neurological and immune disorders, and metabolic syndrome. With the advancement of sphingo-lipidomics and sphingo-genomics, an understanding of the specific roles of ceramide, the quintessential bioactive sphingolipid, in fatty liver disease has taken shape. Two major pathways for ceramide generation, the de novo pathway and the sphingomyelinase pathway are activated in the course of both, the non-alcoholic and the alcoholic, forms of fatty liver disease. The mechanisms of activation of these two pathways are distinct and reflect the different disease etiology in each case; at the same time, common processes impacted by the resulting ceramide overproduction involve lipotoxocity, ER/mitochondrial stress, inflammation, and de-regulation of hepatic lipid metabolism. Studies in human patients and animal models have delineated specific enzymes and ceramide species that are involved at the different stages of the disease, and represent novel pharmaceutical targets for successful management of fatty liver disease.

Alcoholic and non-alcoholic fatty liver disease: Focus on ceramide.

Sphingosine-1-Phosphate Prevents Egress of Hematopoietic Stem Cells From Liver to Reduce Fibrosis

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Sphingosine-1-Phosphate Prevents Egress of Hematopoietic Stem Cells From Liver to Reduce Fibrosis