Human duodenal submucosal glands contain a defined stem/progenitor subpopulation with liver-specific regenerative potential.

BACKGROUND & AIMS: Common precursors for the liver, biliary tree, and pancreas exist at an early stage of development in the definitive endoderm forming the foregut. We have identified and characterised endodermal stem/progenitor cells with regenerative potential persisting in the adult human duodenum. METHODS: Human duodena were obtained from organ donors, and duodenal submucosal gland cells were isolated after removal of the mucosa layer. Cells were cultured on plastic or as organoids and were transplanted into severe combined immunodeficient (SCID) mouse livers. RESULTS: In situ studies of submucosal glands in the human duodenum revealed cells expressing stem/progenitor cell markers that had unique phenotypic traits distinguishable from intestinal crypt cells. Genetic signature studies indicated that the cells are closer to biliary tree stem cells and to definitive endodermal cells than to adult hepatocytes, supporting the interpretation that they are endodermal stem/progenitor cells. In vitro, human duodenal submucosal gland cells demonstrated clonal growth, capability to form organoids, and ability to acquire functional hepatocyte traits. In vivo, transplanted cells engrafted into the livers of immunocompromised mice and differentiated to mature liver cells. In an experimental model of fatty liver, human duodenal submucosal gland cells were able to rescue hosts from liver damage by supporting repopulation and regeneration of the liver. CONCLUSIONS: A cell population with clonal growth and organoid formation capability, which has liver differentiation potency in vitro and in vivo in murine experimental models, is present within adult duodenal submucosal glands. These cells can be isolated, do not require reprogramming, and thus could potentially represent a novel cell source for regenerative medicine of the liver. IMPACT AND IMPLICATIONS: Cell therapies for liver disease could represent an option to support liver function, but the identification of sustainable and viable cell sources is critical. Here, we describe a cell population with organoid formation capability and liver-specific regenerative potential in submucosal glands of the human duodenum. Duodenal submucosal gland cells are isolated from adult organs, do not require reprogramming, and could rescue hepatocellular damage in preclinical models of chronic, but not acute, liver injury. Duodenal submucosal gland cells could represent a potential candidate cell source for regenerative medicine of the liver, but the determination of cell dose and toxicity is needed before clinical testing in humans.

Squamous cell carcinoma of the pancreas: A systematic review and pooled survival analysis.

The diagnosis and treatment of squamous cell carcinoma of the pancreas pose dilemmas in the clinical practice. The present study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to 30th April 2016. A pooled Cox regression analysis was performed to evaluate factors potentially associated with overall survival (OS) and relapse-free survival (RFS). Fifty-four cases of pure squamous cell pancreatic carcinomas were identified in total. The mean age was 61.9 years, and most patients were males (61.1%). The median OS was 7 months. Resectability (p = 0.003) and more recent publication year (p < 0.001) were associated with better OS, as was low/intermediate tumour grade (p = 0.032) with RFS. Despite its poor prognosis, survival rates of pancreatic squamous cell carcinoma seem improved during the recent years; resectability and low/intermediate grade emerged as favourable prognostic factors. Collaborative epidemiological studies are deemed necessary to further validate the results stemming from the published case reports of this rare entity.

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. RESULTS: The HA coating markedly improved the viability, colony formation, and population doubling of hBTSCs in primary cultures, and resulted in a higher expression of integrins that mediate cell attachment to matrix components. When HA-coated hBTSCs were transplanted via the spleen into the liver of immunocompromised mice, the engraftment efficiency increased to 11% with respect to 3% of uncoated cells. Notably, HA-coated hBTSC transplantation in mice resulted in a 10-fold increase of human albumin gene expression in the liver and in a 2-fold increase of human albumin serum levels with respect to uncoated cells. Studies in distant organs showed minimal ectopic cell distribution without differences between HA-coated and uncoated hBTSCs and, specifically, cell seeding in the kidney was excluded. CONCLUSIONS: A ready and economical procedure of HA cell coating greatly enhanced the liver engraftment of transplanted hBTSCs and improved their differentiation toward mature hepatocytes. HA coating could improve outcomes of stem cell therapies of liver diseases and could be immediately translated into the clinic given that GMP-grade HAs are already available for clinical use.

Primary Malignant Melanoma of Renal Pelvis with Extensive Clear Cell Change.

Our presentation illustrates a rare case of primary renal pelvis malignant melanoma in a 35-year-old man. The diagnosis of malignant melanoma was based on immunophenotype and the detection of intracellular melanin pigment. The renal origin was proven by the presence of scattered melanocytes within the urothelium of the pelvis. The tumor exhibited extensive clear cell change that closely mimics clear cell renal cell carcinoma. The patient's clinical history did not disclose any signs of previous melanocytic skin or mucosa lesions. Differential diagnosis includes tumors capable of synthesizing melanin or expressing melanocytic markers.

Acquiring experience in pathology predominantly from what you see, not from what you read: the HIPON e-learning platform.

It is indisputable that nowadays one of the hardest and most important tasks in medicine and especially in medical education, is the conversion of the extensive amount of available data, into medical experience, after a proper analysis. A project under the title "ICT (Information and Communication Technology) eModules on HistoPathology: a useful online tool for students, researchers and professionals - HIPON", co-financed by the Lifelong Learning Program of the Education, Audiovisual and Culture Executive Agency (EACEA), The Commission of the European Union, has been launched at the beginning of 2013. HIPON's purpose is not to provide just another pathology website atlas, but to convey professional experience and thinking in pathology. HIPON has resulted in a well-structured and user-friendly, open resource, multi-language, e-learning platform which, taking advantage of modern image technology, offers medical students, researchers, and professionals a valuable teaching instrument so that they can acquire professional experience in pathology. The mid-term report of HIPON has been favorably evaluated by the EACEA experts who appreciated the potential of our teaching tool in providing the opportunity and the means to acquire medical experience. Through the use of virtual slides, educative videos and microscopic, high resolution, marked images accompanied by relevant questions and answers, HIPON project aims to make end-users able to think as experienced pathologists and become highly efficient in correlating pathologic data with other clinical-laboratory information.