Search

Background & Aims: Extracellular Ca(++) activates cell membrane calcium-sensing receptors (CaRs), leading to renal tubule production of prostaglandins E(2) (PGE(2)), which decrease both sodium reabsorption in the thick ascending limb of Henle's loop and free-water reabsorption in collecting ducts., Aims & Methods: To assess the activity of this diuretic system in experimental cirrhosis, we evaluated renal function, hormonal status, PGE(2) urinary excretion, and renal tissue concentrations of Na(+)-K(+)-2Cl(-) co-transporters (BSC-1) and CaRs in three groups of rats: one group of controls receiving 5% glucose solution (vehicle) intravenously and two groups of rats with CCl(4)-induced preascitic cirrhosis receiving either vehicle or 0.5mg i.v. Poly-l-Arginine (PolyAg), a CaR-selective agonist., Results: Compared to controls, cirrhotic rats showed reduced urine volume and sodium excretion (p<0.05). Western blot analysis revealed reduced CaRs and increased BSC-1 protein content in kidneys of cirrhotic rats compared with controls (all p<0.01). PolyAg-treated cirrhotic rats had their urine and sodium excretion returned to normal; PolyAg also increased renal plasma flow, PGE(2) urinary excretion, and free-water clearance in cirrhotic rats (all p<0.01 v. untreated cirrhotic animals)., Conclusions: In preascitic cirrhosis, sodium retention may be linked to down-regulation of renal CaRs and up-regulation of tubular sodium-retaining channels. Calcimimetic drugs normalize preascitic sodium retention., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Mesenchymal stem cells from bone marrow (MSCs) may have the potential to differentiate in vitro and in vivo into hepatocytes. We investigated whether transplanted human MSCs (hMSCs) may engraft the liver of non-obese diabetic severe combined immuno-deficient (NOD/SCID) mice and differentiate into cells of hepatic lineage., Methods: Ex vivo expanded, highly purified and functionally active hMSCs from bone marrow were transplanted (caudal vein) in sublethally irradiated NOD/SCID mice that were either exposed or not to acute liver injury or submitted to a protocol of chronic injury (single or chronic intraperitoneal injection of CCl(4), respectively). Chimeric livers were analysed for expression of human transcripts and antigens., Results: Liver engraftment of cells of human origin was very low in normal and acutely injured NOD/SCID mice with significantly higher numbers found in chronically injured livers. However, hepatocellular differentiation was relatively rare, limited to a low number of cells (ranging from less than 0.1% to 0.23%) as confirmed by very low or not detectable levels of human transcripts for alpha-fetoprotein, CK18, CK19 and albumin in either normal or injured livers. Finally, a significant number of cells of human origin exhibited a myofibroblast-like morphology., Conclusions: Transplanted hMSCs have the potential to migrate into normal and injured liver parenchyma, particularly under conditions of chronic injury, but differentiation into hepatocyte-like cells is a rare event and pro-fibrogenic potential of hMSC transplant should be not under-evaluated.