Περίληψη:
The liver is the organ with the highest regenerative capacity in the human body. However, various insults, including viral infections, alcohol or drug abuse, and metabolic overload, may cause chronic inflammation and fibrosis, leading to irreversible liver dysfunction. Despite advances in surgery and pharmacological treatments, liver diseases remain a leading cause of death worldwide. To address the shortage of donor liver organs for orthotopic liver transplantation, cell therapy in liver disease has emerged as a promising regenerative treatment. Sources include primary hepatocytes or functional hepatocytes generated from the reprogramming of induced pluripotent stem cells (iPSC). Different types of stem cells have also been employed for transplantation to trigger regeneration, including hematopoietic stem cells (HSCs), mesenchymal stromal cells (MSCs), endothelial progenitor cells (EPCs) as well as adult and fetal liver progenitor cells. HSCs, usually defined by the expression of CD34 and CD133, and MSCs, defined by the expression of CD105, CD73, and CD90, are attractive sources due to their autologous nature, ease of isolation and cryopreservation. The present review focuses on the use of bone marrow HSCs for liver regeneration, presenting evidence for an ongoing crosstalk between the hematopoietic and the hepatic system. This relationship commences during embryogenesis when the fetal liver emerges as the crossroads between the two systems converging the presence of different origins of cells (mesoderm and endoderm) in the same organ. Ample evidence indicates that the fetal liver supports the maturation and expansion of HSCs during development but also later on in life. Moreover, the fact that the adult liver remains one of the few sites for extramedullary hematopoiesis—albeit pathological—suggests that this relationship between the two systems is ongoing. Can, however, the hematopoietic system offer similar support to the liver? The majority of clinical studies using hematopoietic cell transplantation in patients with liver disease report favourable observations. The underlying mechanism—whether paracrine, fusion or transdifferentiation or a combination of the three—remains to be confirmed. © 2022 by the authors.
Συγγραφείς:
Siapati, E.K.
Roubelakis, M.G.
Vassilopoulos, G.
Λέξεις-κλειδιά:
alanine aminotransferase; albumin; alpha fetoprotein; aspartate aminotransferase; bilirubin; carrier protein; colony stimulating factor 1; cytokine; fibroblast growth factor; fms related receptor tyrosine kinase 3 ligand; fusion protein; granulocyte macrophage colony stimulating factor; interleukin 6; scatter factor; somatomedin C; stem cell factor; stromal cell derived factor 1; thrombocyte factor 4; thrombopoietin; transforming growth factor beta; tumor necrosis factor; unclassified drug; vasculotropin; Wnt protein, arteriole; bone marrow; cell transdifferentiation; Child Pugh score; clinical trial (topic); colony forming unit GM; dendritic cell; embryo development; end stage liver disease; endoderm; endothelium cell; extramedullary hematopoiesis; fetus liver; hematopoietic stem cell; hepatic stellate cell; hepatobiliary system; hepatocyte transplantation; human; human cell; human embryonic stem cell; international normalized ratio; Kupffer cell; liver; liver cirrhosis; liver disease; liver regeneration; liver sinusoid; lymphoid progenitor cell; macrophage; megakaryocyte erythroid progenitor; mesodermal cell; mobilization; Model For End Stage Liver Disease Score; myeloid progenitor cell; paracrine signaling; prothrombin time; randomized controlled trial (topic); Review; stem cell niche; stem cell transplantation; adult; hematopoietic stem cell; liver disease; liver regeneration; liver transplantation; living donor, Adult; Hematopoietic Stem Cells; Humans; Liver Diseases; Liver Regeneration; Liver Transplantation; Living Donors
