scholarly journals P001 Establishment of in vitro human model for ulcerative colitis by using human colon organoid culture

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S091-S091
Author(s):  
S Hibiya ◽  
K Tsuchiya ◽  
S Watanabe ◽  
R Nishimura ◽  
T Shirasaki ◽  
...  
1963 ◽  
Vol 117 (5) ◽  
pp. 705-716 ◽  
Author(s):  
Ove Broberger ◽  
Peter Perlmann

By means of immunofluorescent methods it has been shown that sera from children with ulcerative colitis contain antibodies which react with fetal colon cells in tissue culture. 5 out of 13 sera from patients reacted positively when tested for staining antibodies while 12 sera from healthy individuals yielded negative results. The specificity of the staining reactions was confirmed by inhibition experiments. The staining capacity of various sera was correlated to their hemagglutinating titer when tested against phenol-water extracts of human colon. The presence of blood group substances of the ABO system on fetal colon cells in tissue culture could be demonstrated by application of fluorescent H agglutinins from eel. Cross-inhibition experiments indicated that the H agglutinins stained colon antigens which were different from those reacting with the antibodies of ulcerative colitis sera. The reactivity of cultured fetal colon cells with the antibodies in ulcerative colitis sera was retained for up to 12 days, with optimal staining at 4 to 5 days. Reactivity with H agglutinins was present for a longer period, sometimes more than 20 days. Although antigen could be shown to be present on fetal colon cells in tissue culture, exposure of the culture, in the presence of fresh guinea pig serum, to sera from patients with ulcerative colitis did not lead to any visible cytotoxic damage. In order to investigate the possible cytotoxic effect of the sera with a more sensitive technique, freshly explanted fetal colon was dispersed by trypsinization and the cells labeled with 32P-orthophosphate. Subsequently, these cells were exposed to sera, in a final concentration of 30 per cent, from patients or healthy controls in the presence of fresh guinea pig serum (final concentration 15 per cent). Approximately 20 per cent of the cellular isotope was released into the medium within 150 minutes of incubation, but the release was the same in the samples treated either with patients' sera or normal control sera. Thus, under the present conditions, the patients' sera did not exert any specific cytotoxic action on colon cells.


1963 ◽  
Vol 117 (5) ◽  
pp. 717-733 ◽  
Author(s):  
Peter Perlmann ◽  
Ove Broberger

Freshly isolated fetal human colon cells were labeled with 32P-orthophosphate or 14C-amino acids and exposed to white blood cells from children with ulcerative colitis or from healthy controls. Exposure of the colon cells to patients' white cells led to a rapid isotope release, significantly higher than that obtained with normal white cells. After 150 minutes of incubation, 75 per cent of the total isotope present was found in the media of the colitis samples but only 40 per cent in those of the controls. Consistent results were obtained with white blood cells from 14 patients and 18 healthy individuals. Similar results were obtained with either fresh white cells or with white cells aged for 12 to 18 hours and consisting to 60 to 70 per cent of lymphocytes and to 20 to 30 per cent of large mononuclear cells. No specific cytotoxic activity could be conferred onto normal white cells by pretreating them with patients' serum containing antibodies against colon antigen. The cytotoxic action of the patients' white cells was immunologically specific, since no difference from the controls was found in the isotope release when cells from other organs or animals were similarly treated. Preliminary experiments suggested that the patients' white cells could be desensitized by pretreating them with colon extract. For obtaining a significant cytotoxic effect of the patients' white cells, the presence of 10 to 20 per cent of fresh guinea pig or human serum in the incubation medium was required.


2019 ◽  
Author(s):  
Alexandra Sontheimer-Phelps ◽  
David B. Chou ◽  
Alessio Tovaglieri ◽  
Thomas C. Ferrante ◽  
Taylor Duckworth ◽  
...  

ABSTRACTBackground & AimsThe mucus layer in the human colon protects against commensal bacteria and pathogens, and defects in its unique bilayered structure contribute to intestinal disorders, such as ulcerative colitis. However, our understanding of colon physiology is limited by the lack of in vitro models that replicate human colonic mucus layer structure and function. Here, we investigated if combining organ-on-a-chip and organoid technologies can be leveraged to develop a human-relevant in vitro model of colon mucus physiology.MethodsA human colon-on-a-chip (Colon Chip) microfluidic device lined by primary patient-derived colonic epithelial cells was used to recapitulate mucus bilayer formation, and to visualize mucus accumulation in living cultures non-invasively.ResultsThe Colon Chip supports spontaneous goblet cell differentiation and accumulation of a mucus bilayer with impenetrable and penetrable layers, and a thickness similar to that observed in human colon, while maintaining a subpopulation of proliferative epithelial cells. Live imaging of the mucus layer formation on-chip revealed that stimulation of the colonic epithelium with prostaglandin E2, which is elevated during inflammation, causes rapid mucus volume expansion via an NKCC1 ion channel-dependent increase in its hydration state, but no increase in de novo mucus secretion.ConclusionThis study is the first to demonstrate production of colonic mucus with a physiologically relevant bilayer structure in vitro, which can be analyzed in real-time non-invasively. The Colon Chip may offer a new preclinical tool to analyze the role of mucus in human intestinal homeostasis as well as diseases, such as ulcerative colitis and cancer.


2010 ◽  
Vol 48 (05) ◽  
Author(s):  
K Farkas ◽  
Z Rakonczay Jr ◽  
F Nagy ◽  
T Molnár ◽  
Z Szepes ◽  
...  

Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
R Paduch ◽  
M Tomczyk ◽  
A Wiater ◽  
A Dudek ◽  
M Pleszczynska ◽  
...  

1999 ◽  
Vol 38 (04) ◽  
pp. 115-119
Author(s):  
N. Oriuchi ◽  
S. Sugiyama ◽  
M. Kuroki ◽  
Y. Matsuoka ◽  
S. Tanada ◽  
...  

Summary Aim: The purpose of this study was to assess the potential for radioimmunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. Methods: The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. Results: The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tclabeled anti-CEA MAb BW431/261 (31.4 ± 0.95% vs. 11.9 ± 0.55% at 100 ng/mL of soluble CEA, 83.5 ± 2.84% vs. 54.0 ± 2.54% at 107 of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 ± 3.50% ID/g vs. 14.4 ± 3.30% ID/g). 99m-Tcactivity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 ± 2.10% ID/g vs. 8.01 ± 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 ± 1.70% ID/g vs. 8.10 ± 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). Conclusion: 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.


Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
D Krüger ◽  
S Wagner ◽  
CW Hann von Weyhern ◽  
F Zeller ◽  
O Kelber ◽  
...  

2021 ◽  
pp. 113083
Author(s):  
Jessica S. Duprez ◽  
Michael Cohen ◽  
Stephen Li ◽  
Derek Wilson ◽  
Roger H. Brookes ◽  
...  
Keyword(s):  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 493
Author(s):  
Dimitrios T. Trafalis ◽  
Sofia Sagredou ◽  
Panayiotis Dalezis ◽  
Maria Voura ◽  
Stella Fountoulaki ◽  
...  

The fusion of 1,2,4-triazole and 1,3,4-thiadiazole rings results in a class of heterocycles compounds with an extensive range of pharmacological properties. A series of 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles was synthesized and tested for its enzyme inhibition potential and anticancer activity. The results show that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles display potent anticancer properties in vitro against a panel of cancer cells and in vivo efficacy in HT-29 human colon tumor xenograft in CB17 severe combined immunodeficient (SCID) mice. Preliminary mechanistic studies revealed that KA25 and KA39 exhibit time- and concentration-dependent inhibition of Akt Ser-473 phosphorylation. Molecular modeling experiments indicated that 1,2,4-triazolo[3,4-b]-1,2,4-thiadiazoles bind well to the ATP binding site in Akt1 and Akt2. The low acute toxicity combined with in vitro and in vivo anticancer activity render triazolo[3,4-b]thiadiazoles KA25, KA26, and KA39 promising cancer therapeutic agents.


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