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Developmental Cell Feb 2010Embryonic development of the liver has been studied intensely, yielding insights that impact diverse areas of developmental and cell biology. Understanding the... (Review)
Review
Embryonic development of the liver has been studied intensely, yielding insights that impact diverse areas of developmental and cell biology. Understanding the fundamental mechanisms that control hepatogenesis has also laid the basis for the rational differentiation of stem cells into cells that display many hepatic functions. Here, we review the basic molecular mechanisms that control the formation of the liver as an organ.
Topics: Animals; Biliary Tract; Cell Differentiation; Embryonic Stem Cells; Endothelial Cells; Hematopoiesis; Hepatic Stellate Cells; Hepatocytes; Humans; Kupffer Cells; Liver; Mice; Signal Transduction; Transcription, Genetic
PubMed: 20159590
DOI: 10.1016/j.devcel.2010.01.011 -
Nature Medicine Aug 2017The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors...
The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties. We explore the regenerative potential of these organoids in vivo and demonstrate that ECOs self-organize into bile duct-like tubes expressing biliary markers following transplantation under the kidney capsule of immunocompromised mice. In addition, when seeded on biodegradable scaffolds, ECOs form tissue-like structures retaining biliary characteristics. The resulting bioengineered tissue can reconstruct the gallbladder wall and repair the biliary epithelium following transplantation into a mouse model of injury. Furthermore, bioengineered artificial ducts can replace the native CBD, with no evidence of cholestasis or occlusion of the lumen. In conclusion, ECOs can successfully reconstruct the biliary tree, providing proof of principle for organ regeneration using human primary cholangiocytes expanded in vitro.
Topics: Animals; Bile Ducts, Extrahepatic; Biliary Tract; Cell Transplantation; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Cells; Gallbladder; Humans; In Vitro Techniques; Keratin-19; Keratin-7; Mice; Organoids; Regeneration; Secretin; Somatostatin; Tissue Engineering; Tissue Scaffolds; gamma-Glutamyltransferase
PubMed: 28671689
DOI: 10.1038/nm.4360 -
Journal of Hepatology Dec 2022The biliary tract is a complex tubular organ system spanning from the liver to the duodenum. It is the site of numerous acute and chronic disorders, many of unknown... (Review)
Review
The biliary tract is a complex tubular organ system spanning from the liver to the duodenum. It is the site of numerous acute and chronic disorders, many of unknown origin, that are often associated with cancer development and for which there are limited treatment options. Cholangiocytes with proinflammatory capacities line the lumen and specialised types of immune cells reside in close proximity. Recent technological breakthroughs now permit spatiotemporal assessments of immune cells within distinct niches and have increased our understanding of immune cell tissue residency. In this review, a comprehensive overview of emerging knowledge on the immunobiology of the biliary tract system is provided, with a particular emphasis on the role of distinct immune cells in biliary disorders.
Topics: Biliary Tract; Epithelial Cells; Liver
PubMed: 36116989
DOI: 10.1016/j.jhep.2022.08.018 -
Seminars in Liver Disease Feb 2017Despite decades of basic research, biliary diseases remain prevalent, highly morbid, and notoriously difficult to treat. We have, however, dramatically increased our... (Review)
Review
Despite decades of basic research, biliary diseases remain prevalent, highly morbid, and notoriously difficult to treat. We have, however, dramatically increased our understanding of biliary developmental biology, cholangiocyte pathophysiology, and the endogenous mechanisms of biliary regeneration and repair. All of this complex and rapidly evolving knowledge coincides with an explosion of new technological advances in the area of regenerative medicine. New breakthroughs such as induced pluripotent stem cells and organoid culture are increasingly being applied to the biliary system; it is only a matter of time until new regenerative therapeutics for the cholangiopathies are unveiled. In this review, the authors integrate what is known about biliary development, regeneration, and repair, and link these conceptual advances to the technological breakthroughs that are collectively driving the emergence of a new global field in biliary regenerative medicine.
Topics: Animals; Biliary Tract; Biliary Tract Diseases; Humans; Liver; Regeneration; Regenerative Medicine; Stem Cells
PubMed: 28201845
DOI: 10.1055/s-0036-1597818 -
Orphanet Journal of Rare Diseases Nov 2019Primary neuroendocrine carcinomas of the gallbladder and biliary tract are rare, with pure large cell neuroendocrine carcinomas (LCNEC) being exceedingly rare and with a... (Review)
Review
BACKGROUND
Primary neuroendocrine carcinomas of the gallbladder and biliary tract are rare, with pure large cell neuroendocrine carcinomas (LCNEC) being exceedingly rare and with a particularly poor prognosis.
METHODS
We performed a review of published data on biliary tract large cell neuroendocrine carcinomas in PubMed.
RESULTS
Preliminary search revealed over 2000 results but we found only 12 cases of pure large cell neuroendocrine carcinomas of biliary tract noted in literature to date. Because it commonly presents with non-specific symptoms of abdominal pain and jaundice, diagnosis is made after resection with histo-pathological and immunohistochemical analysis. These cancers are particularly aggressive with high recurrence rates, most often presenting with metastasis to regional lymph nodes and/or the liver resulting in a poor prognosis. Overall, complete surgical excision with systemic chemotherapy is the treatment mainstay. If the cancer is unresectable due to multiple metastases, medical management with systemic chemotherapy is the primary treatment modality.
CONCLUSION
The prognosis of hepatobiliary LCNEC remains poor with median survival of only 11 months from initial diagnosis. Studies focusing on high grade neuroendocrine carcinoma are needed to enhance our understanding of biology and therapeutics in this rare but aggressive cancer.
Topics: Aged; Biliary Tract; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Female; Humans; Male; Middle Aged; Prognosis
PubMed: 31752927
DOI: 10.1186/s13023-019-1230-2 -
Frontiers in Immunology 2022The biliary system is comprised of cholangiocytes and plays an important role in maintaining liver function. Under normal conditions, cholangiocytes remain in the... (Review)
Review
The biliary system is comprised of cholangiocytes and plays an important role in maintaining liver function. Under normal conditions, cholangiocytes remain in the stationary phase and maintain a very low turnover rate. However, the robust biliary repair is initiated in disease conditions, and different repair mechanisms can be activated depending on the pathological changes. During biliary disease, immune cells including monocytes, lymphocytes, neutrophils, and mast cells are recruited to the liver. The cellular interactions between cholangiocytes and these recruited immune cells as well as hepatic resident immune cells, including Kupffer cells, determine disease outcomes. However, the role of immune cells in the initiation, regulation, and suspension of biliary repair remains elusive. The cellular processes of cholangiocyte proliferation, progenitor cell differentiation, and hepatocyte-cholangiocyte transdifferentiation during biliary diseases are reviewed to manifest the underlying mechanism of biliary repair. Furthermore, the potential role of immune cells in crucial biliary repair mechanisms is highlighted. The mechanisms of biliary repair in immune-mediated cholangiopathies, inherited cholangiopathies, obstructive cholangiopathies, and cholangiocarcinoma are also summarized. Additionally, novel techniques that could clarify the underlying mechanisms of biliary repair are displayed. Collectively, this review aims to deepen the understanding of the mechanisms of biliary repair and contributes potential novel therapeutic methods for treating biliary diseases.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biliary Tract; Cholangiocarcinoma; Humans; Liver
PubMed: 35432349
DOI: 10.3389/fimmu.2022.866040 -
Comprehensive Physiology Jan 2013Cholangiocytes are epithelial cells that line the intra- and extrahepatic ducts of the biliary tree. The main physiologic function of cholangiocytes is modification of... (Review)
Review
Cholangiocytes are epithelial cells that line the intra- and extrahepatic ducts of the biliary tree. The main physiologic function of cholangiocytes is modification of hepatocyte-derived bile, an intricate process regulated by hormones, peptides, nucleotides, neurotransmitters, and other molecules through intracellular signaling pathways and cascades. The mechanisms and regulation of bile modification are reviewed herein.
Topics: Animals; Bile; Biliary Tract; Epithelial Cells; Humans; Signal Transduction
PubMed: 23720296
DOI: 10.1002/cphy.c120019 -
American Journal of Physiology.... Aug 2017Chronic diseases of the biliary tree (cholangiopathies) represent one of the major unmet needs in clinical hepatology and a significant knowledge gap in liver... (Review)
Review
Chronic diseases of the biliary tree (cholangiopathies) represent one of the major unmet needs in clinical hepatology and a significant knowledge gap in liver pathophysiology. The common theme in cholangiopathies is that the target of the disease is the biliary tree. After damage to the biliary epithelium, inflammatory changes stimulate a reparative response with proliferation of cholangiocytes and restoration of the biliary architecture, owing to the reactivation of a variety of morphogenetic signals. Chronic damage and inflammation will ultimately result in pathological repair with generation of biliary fibrosis and clinical progression of the disease. The hallmark of pathological biliary repair is the appearance of reactive ductular cells, a population of cholangiocyte-like epithelial cells of unclear and likely mixed origin that are able to orchestrate a complex process that involves a number of different cell types, under joint control of inflammatory and morphogenetic signals. Several questions remain open concerning the histogenesis of reactive ductular cells, their role in liver repair, their mechanism of activation, and the signals exchanged with the other cellular elements cooperating in the reparative process. This review contributes to the current debate by highlighting a number of new concepts derived from the study of the pathophysiology of chronic cholangiopathies, such as congenital hepatic fibrosis, biliary atresia, and Alagille syndrome.
Topics: Animals; Bile Duct Diseases; Biliary Tract; Fibrosis; Humans; Liver; Liver Diseases
PubMed: 28526690
DOI: 10.1152/ajpgi.00452.2016 -
Journal of Nuclear Medicine : Official... Jun 2014Cholescintigraphy with (99m)Tc-hepatobiliary radiopharmaceuticals has been an important, clinically useful diagnostic imaging study for almost 4 decades. It continues to... (Review)
Review
Cholescintigraphy with (99m)Tc-hepatobiliary radiopharmaceuticals has been an important, clinically useful diagnostic imaging study for almost 4 decades. It continues to be in much clinical demand; however, the indications, methodology, and interpretative criteria have evolved over the years. This review will emphasize state-of-the-art methodology and diagnostic criteria for various clinical indications, including acute cholecystitis, chronic acalculous gallbladder disease, high-grade and partial biliary obstruction, and the postcholecystectomy pain syndrome, including sphincter-of-Oddi dysfunction and biliary atresia. The review will also emphasize the use of diagnostic pharmacologic interventions, particularly sincalide.
Topics: Biliary Tract; Biliary Tract Diseases; False Positive Reactions; Humans; Liver; Radionuclide Imaging; Reference Standards
PubMed: 24744445
DOI: 10.2967/jnumed.113.131490 -
International Journal of Surgery... Oct 2020For a technically successful liver transplant (LT), secure bile duct anastomosis to prevent biliary complications (BC's) like biliary anastomotic stricture (BAS) and... (Review)
Review
For a technically successful liver transplant (LT), secure bile duct anastomosis to prevent biliary complications (BC's) like biliary anastomotic stricture (BAS) and bile leak (BL) is mandatory. BC's after living donor liver transplantation (LDLT) are relatively more common compared to deceased donor LT (DDLT), particularly owing to surgical factors (small diameter, and/or multiple bile duct openings on the graft), and non-surgical factors (immunologic reactions). Adequate blood supply to the bile duct both in donor and recipient, meticulous anastomotic technique, mucosal eversion for better approximation thus avoiding lesser fibrosis, proper use of internal or external stent drainage, and tension-free anastomosis, may contribute to the decrease of BC's after LDLT. Further, if BC's are not dealt with in a timely manner, these could progressively lead to severe morbidities and even mortality. While the endoscopic approach is preferred initially to deal with biliary leaks or strictures, the more invasive percutaneous approach may be required in case of endoscopic failure. Dedicated and experienced endoscopists, and interventional radiologists are key members of the multidisciplinary team in a successful LDLT program. In this review, we have tried to summarize current concepts in surgical techniques of biliary reconstruction in LDLT, incidence and risk factors for BC's, and principles followed to try and reduce the incidence of the same.
Topics: Bile Ducts; Biliary Tract Diseases; Biliary Tract Surgical Procedures; Humans; Liver Transplantation; Living Donors; Plastic Surgery Procedures; Risk Factors
PubMed: 32387205
DOI: 10.1016/j.ijsu.2020.04.069