Conversion of pancreatic cells to hepatocytes

2002 ◽  
Vol 30 (2) ◽  
pp. 51-54 ◽  
Author(s):  
David Tosh ◽  
Chia-Ning Shen ◽  
Jonathan M. W. Slack

Transdifferentiation is the name used to describe the conversion of one differentiated cell type to another. During development, the liver and pancreas arise from the same region of the endoderm and cells from the two organs can transdifferentiate in the adult under different experimental procedures. We have produced two in vitro models for the transdifferentiation of pancreatic cells to hepatocytes. The first utilizes a pancreatic exocrine cell line AR42J-B13 and the second comprises cultures of mouse embryonic pancreas. We have analysed the pancreatic hepatocytes and they express a range of liver markers including albumin, transferrin and transthyretin. We also present evidence for (i) the molecular mechanism which regulates the conversion between pancreas and liver and (ii) the cellular basis of the switch in phenotype.

2013 ◽  
Vol 7 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Hodik M ◽  
Lukinius A ◽  
Korsgren O ◽  
Frisk G

Human Enteroviruses (HEVs) have been implicated in human pancreatic diseases such as pancreatitis and type 1 diabetes (T1D). Human studies are sparse or inconclusive and our aim was to investigate the tropism of two strains of Coxsackie B virus 5 (CBV-5) in vitro to primary human pancreatic cells. Virus replication was measured with TCID50 titrations of aliquots of the culture medium at different time points post inoculation. The presence of virus particles or virus proteins within the pancreatic cells was studied with immunohistochemistry (IHC) and electron microscopy (EM). None of the strains replicated in the human exocrine cell clusters, in contrast, both strains replicated in the endocrine islets of Langerhans. Virus particles were found exclusively in the endocrine cells, often in close association with insulin granules. In conclusion, CBV-5 can replicate in human endocrine cells but not in human exocrine cells, thus they might not be the cause of pancreatitis in humans. The association of virus with insulin granules might reflect the use of these as replication scaffolds.


1994 ◽  
Vol 22 (3) ◽  
pp. 168-174
Author(s):  
Hasso Seibert ◽  
Michael Gulden ◽  
Jens-Uwe Voss

If “cell toxicology” is defined as the discipline aimed at studying the general principles of chemical interference with cellular structures and/or functions, then “comparative cell toxicology” may be defined as the study of the variety of responses to xenobiotics using: (a) different endpoints within one cell type; (b) cell types from different tissues from one species; and (c) homologous cell types from different species. If the full potential of in vitro models for toxicity testing is to be realised and the scientific basis for hazard assessment improved, then comparative cell toxicological approaches have to be developed further. In the present paper, an approach using different in vitro systems is described. The approach is aimed at the assessment of the basic toxicological characteristics of chemicals.


2021 ◽  
Vol 118 (26) ◽  
pp. e2019415118
Author(s):  
Mark-Phillip Pebworth ◽  
Jayden Ross ◽  
Madeline Andrews ◽  
Aparna Bhaduri ◽  
Arnold R. Kriegstein

Studies of the spatiotemporal, transcriptomic, and morphological diversity of radial glia (RG) have spurred our current models of human corticogenesis. In the developing cortex, neural intermediate progenitor cells (nIPCs) are a neuron-producing transit-amplifying cell type born in the germinal zones of the cortex from RG. The potential diversity of the nIPC population, that produces a significant portion of excitatory cortical neurons, is understudied, particularly in the developing human brain. Here we explore the spatiotemporal, transcriptomic, and morphological variation that exists within the human nIPC population and provide a resource for future studies. We observe that the spatial distribution of nIPCs in the cortex changes abruptly around gestational week (GW) 19/20, marking a distinct shift in cellular distribution and organization during late neurogenesis. We also identify five transcriptomic subtypes, one of which appears at this spatiotemporal transition. Finally, we observe a diversity of nIPC morphologies that do not correlate with specific transcriptomic subtypes. These results provide an analysis of the spatiotemporal, transcriptional, and morphological diversity of nIPCs in developing brain tissue and provide an atlas of nIPC subtypes in the developing human cortex that can benchmark in vitro models of human development such as cerebral organoids and help inform future studies of how nIPCs contribute to cortical neurogenesis.


1971 ◽  
Vol 48 (3) ◽  
pp. 503-522 ◽  
Author(s):  
James D. Jamieson ◽  
George E. Palade

We have examined, in the pancreatic exocrine cell, the metabolic requirements for the conversion of condensing vacuoles into zymogen granules and for the discharge of the contents of zymogen granules. To study condensing vacuole conversion, we pulse labeled guinea pig pancreatic slices for 4 min with leucine-3H and incubated them in chase medium for 20 min to allow labeled proteins to reach condensing vacuoles. Glycolytic and respiratory inhibitors were then added and incubation continued for 60 min to enable labeled proteins to reach granules in control slices. Electron microscope radioautography of cells or of zymogen granule pellets from treated slices showed that a large proportion of prelabeled condensing vacuoles underwent conversion in the presence of the combined inhibitors. Osmotic fragility studies on zymogen granule suspensions suggest that condensation may result from the aggregation of secretory proteins in an osmotically inactive form. Discharge was studied using an in vitro radioassay based on the finding that prelabeled zymogen granules can be induced to release their labeled contents to the incubation medium by carbamylcholine or pancreozymin. Induced discharge is not affected if protein synthesis is blocked by cycloheximide for up to 2 hr, but is strictly dependent on respiration. The data indicate that transport and discharge do not require the pari passu synthesis of secretory or nonsecretory proteins (e.g. membrane proteins), suggesting that the cell may reutilize its membranes during the secretory process. The energy requirements for zymogen discharge may be related to the fusion-fission of the granule membrane with the apical plasmalemma.


2020 ◽  
Vol 8 (7) ◽  
pp. 1053
Author(s):  
Célia Chamignon ◽  
Virgile Guéneau ◽  
Sonia Medina ◽  
Julien Deschamps ◽  
Angel Gil-Izquierdo ◽  
...  

Over the last 20 years, Lactobacillus species inhabiting the gastrointestinal tract (GIT) have received much attention, and their health-promoting properties are now well-described. Probiotic effects cannot be generalized, and their uses cover a wide range of applications. It is thus important to proceed to an accurate selection and evaluation of probiotic candidates. We evaluate the probiotic potential of six strains of Lactobacillus in different in vitro models representing critical factors of either survival, efficacy, or both. We characterized the strains for their ability to (i) modulate intestinal permeability using transepithelial electrical resistance (TEER), (ii) form biofilms and resist stressful conditions, and (iii) produce beneficial host and/or bacteria metabolites. Our data reveal the specificity of Lactobacillus strains to modulate intestinal permeability depending on the cell type. The six isolates were able to form spatially organized biofilms, and we provide evidence that the biofilm form is beneficial in a strongly acidic environment. Finally, we demonstrated the ability of the strains to produce γ-aminobutyric acid (GABA) that is involved in the gut-brain axis and beneficial enzymes that promote the bacterial tolerance to bile salts. Overall, our study highlights the specific properties of Lactobacillus strains and their possible applications as biofilms.


2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Stina Hellman

AbstractEnteroid cultures are three-dimensional in vitro models that reflect the cellular composition and architecture of the small intestine. One limitation with the enteroid conformation is the enclosed lumen, making it difficult to expose the apical surface of the epithelium to experimental treatments. The present study was therefore conducted to generate cultures of equine enteroids and to develop methods for culture of enteroid-derived cells on a two-dimensional plane, enabling easy access to the apical surface of the epithelium. Equine enteroids were established from small intestinal crypts within 7–9 days of culture. Transcriptional analysis of cell type markers confirmed the presence of enterocytes, stem-, Paneth-, proliferative-, enteroendocrine-, goblet- and tuft cells. This cellular composition was maintained over multiple passages, showing that the enteroids can be kept for prolonged periods. The transfer from 3D enteroids to 2D monolayers slightly modified the relative expression levels of the cell type markers, indicating a decrease of goblet- and Paneth cells in the monolayers. Stimulation with the TLR2, 3 and 4 agonists Pam3CSK4, Poly I:C and LPS, respectively, induced the pro-inflammatory cytokines TNF-α and IL-8, while the TLR5 agonist FliC only induced TNF-α. In addition, an up-regulation of TGF-β, IL-33 and IFN-β was recorded after exposure to lipofected Poly I:C that also affected the monolayer integrity. Thus, the equine enteroid-derived 2D monolayers described in the present study show both genetic and functional similarities with the equine intestine making it an interesting in vitro model for studies demanding access to the apical surface, e.g. in studies of host-microbe interactions.


Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.


2014 ◽  
Vol 226 (06) ◽  
Author(s):  
D William ◽  
M Linnebacher ◽  
CF Classen

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