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Current Opinion in Endocrinology,... Apr 2014We highlight some of the major recent advances in characterizing human pancreas development and endocrine cell differentiation. (Review)
Review
PURPOSE OF REVIEW
We highlight some of the major recent advances in characterizing human pancreas development and endocrine cell differentiation.
RECENT FINDINGS
Extensive research efforts have helped to define crucial events in the mouse pancreas organogenesis. Information gained from these studies was used to develop human embryonic stem cell (hESC) differentiation protocols with the goal of generating functional glucose-responsive, insulin-producing human β-cells. In spite of remarkable progress in hESC differentiation, current protocols based on mouse developmental biology can produce human β-cells only in vivo. New differentiation markers and recently generated reagents may provide an unprecedented opportunity to develop a high-density expression map of human fetal pancreas and pancreatic islets that could serve as a reference point for in vitro hESC differentiation.
SUMMARY
Integrating an increased knowledge of human pancreas development into hESC differentiation protocols has the potential to greatly advance our ability to generate functional insulin-producing cells for β-cell replacement therapy.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Embryonic Stem Cells; Endocrine System; Glucose; Humans; Insulin-Secreting Cells; Mice; Organogenesis; Pancreas; Signal Transduction
PubMed: 24569548
DOI: 10.1097/MED.0000000000000047 -
Abdominal Radiology (New York) Aug 2022Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic... (Review)
Review
Percutaneous pancreatic interventions performed by abdominal radiologists play important diagnostic and therapeutic roles in the management of a wide range of pancreatic pathology. While often performed with endoscopy, pancreatic mass biopsy obtained via a percutaneous approach may serve as the only feasible option for diagnosis in patients with post-surgical anatomy, severe cardiopulmonary conditions, or prior non-diagnostic endoscopic attempts. Biopsy of pancreatic transplants are commonly performed percutaneously due to inaccessible location of the allograft by endoscopy, usually in the right lower quadrant or pelvis. Percutaneous drainage of collections in acute pancreatitis is primarily indicated for infection with clinical deterioration and may be performed alone or in combination with endoscopic drainage. Post-surgical pancreatic collections related to pancreatic duct fistula or leak also often warrant therapeutic percutaneous drainage. Knowledge of appropriate indications, strategies of approach, technique, and complications associated with these procedures is critical for a successful clinical practice.
Topics: Acute Disease; Biopsy; Drainage; Endoscopy, Gastrointestinal; Humans; Pancreas; Pancreatic Ducts; Pancreatitis; Treatment Outcome
PubMed: 34410433
DOI: 10.1007/s00261-021-03244-z -
International Journal of Molecular... Dec 2015The Notch signaling pathway plays a significant role in embryonic cell fate determination and adult tissue homeostasis. Various studies have demonstrated the deep... (Review)
Review
The Notch signaling pathway plays a significant role in embryonic cell fate determination and adult tissue homeostasis. Various studies have demonstrated the deep involvement of Notch signaling in the development of the pancreas and the lateral inhibition of Notch signaling in pancreatic progenitor differentiation and maintenance. The targeted inactivation of the Notch pathway components promotes premature differentiation of the endocrine pancreas. However, there is still the contrary opinion that Notch signaling specifies the endocrine lineage. Here, we review the current knowledge of the Notch signaling pathway in pancreatic development and its crosstalk with the Wingless and INT-1 (Wnt) and fibroblast growth factor (FGF) pathways.
Topics: Animals; Fibroblast Growth Factors; Humans; Pancreas; Receptors, Notch; Signal Transduction
PubMed: 26729103
DOI: 10.3390/ijms17010048 -
Diabetes Oct 2021β-Cells in the islet of Langerhans have a central role in maintaining energy homeostasis. Understanding the physiology of β-cells and other islet cells requires a deep... (Review)
Review
β-Cells in the islet of Langerhans have a central role in maintaining energy homeostasis. Understanding the physiology of β-cells and other islet cells requires a deep understanding of their structural and functional organization, their interaction with vessels and nerves, the layout of paracrine interactions, and the relationship between subcellular compartments and protein complexes inside each cell. These elements are not static; they are dynamic and exert their biological actions at different scales of time. Therefore, scientists must be able to investigate (and visualize) short- and long-lived events within the pancreas and β-cells. Current technological advances in microscopy are able to bridge multiple spatiotemporal scales in biology to reveal the complexity and heterogeneity of β-cell biology. Here, I briefly discuss the historical discoveries that leveraged microscopes to establish the basis of β-cell anatomy and structure, the current imaging platforms that allow the study of islet and β-cell biology at multiple scales of resolution, and their challenges and implications. Lastly, I outline how the remarkable longevity of structural elements at different scales in biology, from molecules to cells to multicellular structures, could represent a previously unrecognized organizational pattern in developing and adult β-cells and pancreas biology.
Topics: Animals; Cell Self Renewal; Cell Survival; Homeostasis; Humans; Insulin-Secreting Cells; Islets of Langerhans; Pancreas; Time Factors
PubMed: 34593534
DOI: 10.2337/dbi21-0008 -
Seminars in Cell & Developmental Biology Aug 2012Recent advances in generating pancreatic cell types from human pluripotent stem cells has depended on our knowledge of the developmental processes that regulate pancreas... (Review)
Review
Recent advances in generating pancreatic cell types from human pluripotent stem cells has depended on our knowledge of the developmental processes that regulate pancreas development in vivo. The developmental events between gastrulation and formation of the embryonic pancreatic primordia are both rapid and dynamic and studies in frog, fish, chick, and mouse have identified the molecular basis of how the pancreas develops from multipotent endoderm progenitors. Here, we review the current status of our understanding of molecular mechanisms that control endoderm formation, endoderm patterning, and pancreas specification and highlight how these discoveries have allowed for the development of robust methods to generate pancreatic cells from human pluripotent stem cells.
Topics: Animals; Endoderm; Humans; Organogenesis; Pancreas; Pluripotent Stem Cells; Signal Transduction
PubMed: 22743233
DOI: 10.1016/j.semcdb.2012.06.009 -
Molecular and Cellular Endocrinology Dec 2021Though embryonic pancreas progenitors are well characterised, the existence of stem/progenitor cells in the postnatal mammalian pancreas has been long debated, mainly... (Review)
Review
Though embryonic pancreas progenitors are well characterised, the existence of stem/progenitor cells in the postnatal mammalian pancreas has been long debated, mainly due to contradicting results on regeneration after injury or disease in mice. Despite these controversies, sequencing advancements combined with lineage tracing and organoid technologies indicate that homeostatic and trigger-induced regenerative responses in mice could occur. The presence of putative progenitor cells in the adult pancreas has been proposed during homeostasis and upon different stress challenges such as inflammation, tissue damage and oncogenic stress. More recently, single cell transcriptomics has revealed a remarkable heterogeneity in all pancreas cell types, with some cells showing the signature of potential progenitors. In this review we provide an overview on embryonic and putative adult pancreas progenitors in homeostasis and disease, with special emphasis on in vitro culture systems and scRNA-seq technology as tools to address the progenitor nature of different pancreatic cells.
Topics: Animals; Cell Differentiation; Gene Regulatory Networks; Homeostasis; Humans; Pancreas; Pancreatic Diseases; RNA-Seq; Regenerative Medicine; Single-Cell Analysis; Stem Cells
PubMed: 34543699
DOI: 10.1016/j.mce.2021.111459 -
The British Journal of Radiology Jul 2019MRI plays an important role in the clinical management of pancreatic disorders and interpretation is reliant on qualitative assessment of anatomy. Conventional sequences... (Review)
Review
MRI plays an important role in the clinical management of pancreatic disorders and interpretation is reliant on qualitative assessment of anatomy. Conventional sequences capturing pancreatic structure can however be adapted to yield quantitative measures which provide more diagnostic information, with a view to increasing diagnostic accuracy, improving patient stratification, providing robust non-invasive outcome measures for therapeutic trials and ultimately personalizing patient care. In this review, we evaluate the use of established techniques such as secretin-enhanced MR cholangiopancreatography, diffusion-weighted imaging, , * and fat fraction mapping, but also more experimental methods such as MR elastography and arterial spin labelling, and their application to the assessment of diffuse pancreatic disease (including chronic, acute and autoimmune pancreatitis/IgG4 disease, metabolic disease and iron deposition disorders) and cystic/solid focal pancreatic masses. Finally, we explore some of the broader challenges to their implementation and future directions in this promising area.
Topics: Humans; Magnetic Resonance Imaging; Pancreas; Pancreatic Diseases
PubMed: 30982337
DOI: 10.1259/bjr.20180941 -
Journal of Ultrasound Sep 2019The pancreas is easily investigated in children thanks to the relative lack of fat tissue and the large left hepatic lobe with an optimal acoustic window. The use of... (Review)
Review
The pancreas is easily investigated in children thanks to the relative lack of fat tissue and the large left hepatic lobe with an optimal acoustic window. The use of high frequency, even linear transducers, usually results in detailed images of all pancreatic areas. A wide spectrum of pancreatic pathologic conditions can be identified and monitored at ultrasound although they are relatively uncommon during childhood compared to the adult. In this paper we briefly review the anatomy, technique, and sonographic aspects of normal and pathological pediatric pancreas.
Topics: Anatomic Variation; Child; Humans; Pancreas; Pancreatic Diseases; Reference Values; Ultrasonography
PubMed: 30552664
DOI: 10.1007/s40477-018-0348-8 -
Nature Biomedical Engineering Nov 2022A lack of comprehensive mapping of ganglionic inputs into the pancreas and of technology for the modulation of the activity of specific pancreatic nerves has hindered...
A lack of comprehensive mapping of ganglionic inputs into the pancreas and of technology for the modulation of the activity of specific pancreatic nerves has hindered the study of how they regulate metabolic processes. Here we show that the pancreas-innervating neurons in sympathetic, parasympathetic and sensory ganglia can be mapped in detail by using tissue clearing and retrograde tracing (the tracing of neural connections from the synapse to the cell body), and that genetic payloads can be delivered via intrapancreatic injection to target sites in efferent pancreatic nerves in live mice through optimized adeno-associated viruses and neural-tissue-specific promoters. We also show that, in male mice, the targeted activation of parasympathetic cholinergic intrapancreatic ganglia and neurons doubled plasma-insulin levels and improved glucose tolerance, and that tolerance was impaired by stimulating pancreas-projecting sympathetic neurons. The ability to map the peripheral ganglia innervating the pancreas and to deliver transgenes to specific pancreas-projecting neurons will facilitate the examination of ganglionic inputs and the study of the roles of pancreatic efferent innervation in glucose metabolism.
Topics: Mice; Male; Animals; Virus Activation; Pancreas; Neurons; Synapses; Glucose
PubMed: 35835995
DOI: 10.1038/s41551-022-00909-y -
Molecular Metabolism Aug 2023Over the last decades, various approaches have been explored to restore sufficient β-cell mass in diabetic patients. Stem cells are certainly an attractive source of... (Review)
Review
BACKGROUND
Over the last decades, various approaches have been explored to restore sufficient β-cell mass in diabetic patients. Stem cells are certainly an attractive source of new β-cells, but an alternative option is to induce the endogenous regeneration of these cells.
SCOPE OF REVIEW
Since the exocrine and endocrine pancreatic glands have a common origin and a continuous crosstalk unites the two, we believe that analyzing the mechanisms that induce pancreatic regeneration in different conditions could further advance our knowledge in the field. In this review, we summarize the latest evidence on physiological and pathological conditions associated with the regulation of pancreas regeneration and proliferation, as well as the complex and coordinated signaling cascade mediating cell growth.
MAJOR CONCLUSIONS
Unraveling the mechanisms involved in intracellular signaling and regulation of pancreatic cell proliferation and regeneration may inspire future investigations to discover potential strategies to cure diabetes.
Topics: Humans; Diabetes Mellitus, Type 2; Islets of Langerhans; Pancreas; Insulin-Secreting Cells; Regeneration
PubMed: 37321370
DOI: 10.1016/j.molmet.2023.101754