Cholest-4,6-Dien-3-One Promote Epithelial-To-Mesenchymal Transition (EMT) in Biliary Tree Stem/Progenitor Cell Cultures In Vitro.

Human biliary tree stem/progenitor cells (hBTSCs), reside in peribiliary glands, are mainly stimulated by primary sclerosing cholangitis (PSC) and cholangiocarcinoma. In these pathologies, hBTSCs displayed epithelial-to-mesenchymal transition (EMT), senescence characteristics, and impaired differentiation. Here, we investigated the effects of cholest-4,6-dien-3-one, an oxysterol involved in cholangiopathies, on hBTSCs biology.

Peribiliary Gland Niche Participates in Biliary Tree Regeneration in Mouse and in Human Primary Sclerosing Cholangitis.

Background And Aims: Mechanisms underlying the repair of extrahepatic biliary tree (EHBT) after injury have been scarcely explored. The aims of this study were to evaluate, by using a lineage tracing approach, the contribution of peribiliary gland (PBG) niche in the regeneration of EHBT after damage and to evaluate, in vivo and in vitro, the signaling pathways involved.

Approach And Results: Bile duct injury was induced by the administration of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 14 days to Krt19 TdTomato mice.

Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells.

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG).

Neoplastic Transformation of the Peribiliary Stem Cell Niche in Cholangiocarcinoma Arisen in Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a chronic inflammatory cholangiopathy frequently complicated by cholangiocarcinoma (CCA). Massive proliferation of biliary tree stem/progenitor cells (BTSCs), expansion of peribiliary glands (PBGs), and dysplasia were observed in PSC. The aims of the present study were to evaluate the involvement of PBGs and BTSCs in CCA which emerged in PSC patients.

Cryopreservation protocol for human biliary tree stem/progenitors, hepatic and pancreatic precursors.

Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans.

Hyaluronan coating improves liver engraftment of transplanted human biliary tree stem/progenitor cells.

Background: Cell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver.

Methods: We developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo.

Appraisal of transplant-related stressors, coping strategies, and psychosocial adjustment following kidney transplantation.

This study examined the relations between appraisal of transplant-related stressors, coping, and adjustment dimensions following kidney transplantation (KT). Two models were tested: (1) the main effects model proposing that stress appraisal and coping strategies are directly associated with adjustment dimensions; and (2) the moderating model of stress proposing that each coping strategy interacts with stress appraisal. Importantly, there is a lack of research examining the two models simultaneously among recipients of solid organ transplantation.

Progenitor cell niches in the human pancreatic duct system and associated pancreatic duct glands: an anatomical and immunophenotyping study.

Pancreatic duct glands (PDGs) are tubule-alveolar glands associated with the pancreatic duct system and can be considered the anatomical counterpart of peribiliary glands (PBGs) found within the biliary tree. Recently, we demonstrated that endodermal precursor niches exist fetally and postnatally and are composed functionally of stem cells and progenitors within PBGs and of committed progenitors within PDGs. Here we have characterized more extensively the anatomy of human PDGs as novel niches containing cells with multiple phenotypes of committed progenitors.

Chylous Leakage After a Laparoscopic Live-Donor Nephrectomy: Case Report and Literature Review.

Laparoscopic donor nephrectomy is an established operation for organ procurement in living-donor transplant. Minimal access approach for organ procurement from living donors ensures early convalescence and improved patient participation. Chylous leakage is a rare complication of laparoscopic living-donor nephrectomy.

Adult Human Biliary Tree Stem Cells Differentiate to β-Pancreatic Islet Cells by Treatment with a Recombinant Human Pdx1 Peptide.

Generation of β-pancreatic cells represents a major goal in research. The aim of this study was to explore a protein-based strategy to induce differentiation of human biliary tree stem cells (hBTSCs) towards β-pancreatic cells. A plasmid containing the sequence of the human pancreatic and duodenal homeobox 1 (PDX1) has been expressed in E.

Activation of biliary tree stem cells within peribiliary glands in primary sclerosing cholangitis.

Background & Aims: Primary sclerosing cholangitis (PSC) is characterised by fibro-stenosing strictures involving extrahepatic and/or large intrahepatic bile ducts. Mechanisms leading to bile duct injury are poorly understood. We aimed to study the biliary tree stem cell compartment located in peribiliary glands of extrahepatic and large intrahepatic bile ducts and its role in the pathogenesis of biliary fibrosis in PSC.

Cerebral Lymphoma in a Kidney Transplant: A Case Report.

Posttransplant lymphoproliferative disorder is a serious complication during a solid-organ transplant. A 28-year-old Asiatic man developed a cerebral lesion that was considered an abscess, while undergoing a kidney transplant. The lesion diameter did not go down with antibiotic therapy, so he underwent a complete surgical mass excision.

Renal Papillary Carcinoma Developed in a Kidney Transplant Recipient With Late IgA-Nephropathy.

With improvements in immunosuppressive therapy, patient and graft survival in renal transplant recipients have been prolonged. Increasing donor age and patient survival rates have been related to an increase in the number of de novo tumors. Posttransplant malignancy in these patients is an important cause of graft loss and death in these patients.

Cholangiocarcinoma: increasing burden of classifications.

Cholangiocarcinoma (CCA) is a very heterogeneous cancer from any point of view, including epidemiology, risk factors, morphology, pathology, molecular pathology, modalities of growth and clinical features. Given this heterogeneity, a uniform classification respecting the epidemiologic, pathologic and clinical needs is currently lacking. In this manuscript we discussed the different proposed classifications of CCA in relation with recent advances in pathophysiology and biology of this cancer.

Role of BK virus infection in end-stage renal disease patients waiting for kidney transplantation--viral replication dynamics from pre- to post-transplant.

We report the prevalence of BK virus (BKV) infection before renal transplantation and the dynamics of BKV viremia from pre- to post-transplantation. We assessed 60 kidney transplanted patients from a single cohort in Italy, treated with identical immunosuppressive therapy, for BK viremia at pre-transplantation, 12 h, and three and six months post-transplantation. Polymerase chain reaction showed that the prevalence of plasma BKV replication--considered a marker of infection--was 20% in pre-transplant patients.

The role of transplant-related stressors and social support in the development of anxiety among renal transplant recipients: the direct and buffering effects.

Several studies have shown a relevant presence of anxiety feelings among renal transplant patients. This study examines the impact of transplant-related stress and social support on anxiety. Two hypotheses were examined: H1: High transplant-related stressors and low social support are related to high anxiety (additive hypothesis); H2: Social support moderates the detrimental impact of transplant-related stressors on anxiety (buffer hypothesis).

Bilateral ex vivo repair and kidney autotransplantation for complex renal artery aneurysms: a case report and literature review.

We report the surgical management of a bilateral renal artery aneurysm diagnosed in a 41-year-old patient with a history of recurrent abdominal pain. The preoperative contrast-enhanced computed tomography showed a complex saccular aneurysm on both renal arteries within the renal hilum. The characteristics of aneurysms precluded endovascular procedures, and a double-step bilateral ex vivo reconstruction with kidney autotransplantation was planned.

Graft macrosteatosis and time of T-tube removal as risk factors for biliary strictures after liver transplantation.

Biliary strictures (BS) remain a significant problem following liver transplantation (LT), representing an important cause of morbidity. The purpose of this follow-up study was to evaluate the incidence and risk factors associated with BS after LT. From 2001 to 2009, 244 consecutive patients underwent LT at our center.

Surgical treatment of esophageal carcinoma with curative intent: analysis of a single center experience.

Background: We retrospectively reviewed our series of 76 patients who underwent esophagectomy, with curative intent, for esophageal carcinoma over the last 10 years.

Method: The mean age was 60 years ranging between 46 to 76 years. Fifty-seven patients had a squamous cell carcinoma and 19 patients had an adenocarcinoma.

Use of elderly donors for liver transplantation: has the limit been reached?

Background And Aim: Several solutions have been proposed for the minimization of both organ shortage and prolonged waiting time for liver transplantation (LT): expansion of the donor pool using elderly donors represents a possible solution. However, it is still not fully explained if the use of "extreme" donors could cause inacceptable post-transplant adjunctive risks. The aim of the study is to evaluate the impact of donor age on post-LT patient and graft survival.

Biliary tree stem/progenitor cells in glands of extrahepatic and intraheptic bile ducts: an anatomical in situ study yielding evidence of maturational lineages.

Stem/progenitors have been identified intrahepatically in the canals of Hering and extrahepatically in glands of the biliary tree. Glands of the biliary tree (peribiliary glands) are tubulo-alveolar glands with mucinous and serous acini, located deep within intrahepatic and extrahepatic bile ducts. We have shown that biliary tree stem/progenitors (BTSCs) are multipotent, giving rise in vitro and in vivo to hepatocytes, cholangiocytes or pancreatic islets.

Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets.

Unlabelled: Multipotent stem/progenitors are present in peribiliary glands of extrahepatic biliary trees from humans of all ages and in high numbers in hepato-pancreatic common duct, cystic duct, and hilum. They express endodermal transcription factors (e.g.

Prostate apoptosis response-4 is expressed in normal cholangiocytes, is down-regulated in human cholangiocarcinoma, and promotes apoptosis of neoplastic cholangiocytes when induced pharmacologically.

Prostate apoptosis response-4 (Par-4) is a tumor suppressor protein that sensitizes cells to apoptosis; therefore, Par-4 modulation has therapeutic potential. No data currently exist on Par-4 expression in cholangiocarcinoma (CCA). We evaluated the expression of Par-4 in normal and neoplastic cholangiocytes and the effects of its pharmacological or genetic modulation.