PMID- 34354753
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210807
IS  - 1687-966X (Print)
IS  - 1687-9678 (Electronic)
VI  - 2021
DP  - 2021
TI  - Development of a Human Intestinal Organoid Model for In Vitro Studies on Gut 
      Inflammation and Fibrosis.
PG  - 9929461
LID - 10.1155/2021/9929461 [doi]
LID - 9929461
AB  - Inflammatory Bowel Diseases (IBDs) are characterized by chronic intestinal 
      inflammation and fibrosis, the latter being the predominant denominator for 
      long-term complications. Epithelial and mesenchymal 2D cultures are highly 
      utilized in vitro models for the preclinical evaluation of anti-inflammatory and 
      antifibrotic therapies. More recently, human intestinal organoids (HIOs), a new 
      3D in vitro model derived from pluripotent stem cells, have the advantage to 
      closely resemble the architecture of the intestinal mucosa. However, the 
      appropriate timing for the study of inflammatory and fibrotic responses, during 
      HIO development, has not been adequately investigated. We developed HIOs from the 
      human embryonic stem cell line, H1, and examined the expression of mesenchymal 
      markers during their maturation process. We also investigated the effect of 
      inflammatory stimuli on the expression of fibrotic and immunological mediators. 
      Serial evaluation of the expression of mesenchymal and extracellular matrix (ECM) 
      markers revealed that HIOs have an adequately developed mesenchymal component, 
      which gradually declines through culture passages. Specifically, CD90, collagen 
      type I, collagen type III, and fibronectin were highly expressed in early 
      passages but gradually diminished in late passages. The proinflammatory cytokines 
      IL-1alpha and TNF-alpha induced the mRNA expression of fibronectin, collagen types I and 
      III, tissue factor (TF), and alpha-smooth muscle actin (alpha-SMA) primarily in early 
      passages. Similarly, HIOs elicited strong mRNA and protein mesenchymal (CXCL10) 
      and epithelial (CXCL1, CCL2, CXCL8, and CCL20) chemokine responses in early but 
      not late passages. In contrast, the epithelial tight junction components, CLDN1 
      and JAMA, responded to inflammatory stimulation independently of the culture 
      passage. Our findings indicate that this HIO model contains a functional 
      mesenchymal component, during early passages, and underline the significance of 
      the mesenchymal cells' fitness in inflammatory and fibrotic responses. Therefore, 
      we propose that this model is suitable for the study of epithelial-mesenchymal 
      interactions in early passages when the mesenchymal component is active.
CI  - Copyright (c) 2021 Leonidas Kandilogiannakis et al.
FAU - Kandilogiannakis, Leonidas
AU  - Kandilogiannakis L
AUID- ORCID: 0000-0002-5982-4210
AD  - Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 
      Alexandroupolis, Greece.
FAU - Filidou, Eirini
AU  - Filidou E
AUID- ORCID: 0000-0002-7146-4684
AD  - Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 
      Alexandroupolis, Greece.
FAU - Drygiannakis, Ioannis
AU  - Drygiannakis I
AUID- ORCID: 0000-0001-5845-2040
AD  - Gastroenterology and Hepatology Research Laboratory, Medical School, University 
      of Crete, Heraklion, Greece.
FAU - Tarapatzi, Gesthimani
AU  - Tarapatzi G
AUID- ORCID: 0000-0002-6877-5991
AD  - Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 
      Alexandroupolis, Greece.
FAU - Didaskalou, Stylianos
AU  - Didaskalou S
AUID- ORCID: 0000-0001-5932-9626
AD  - Laboratory of Molecular Cell Biology, Department of Molecular Biology and 
      Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Koffa, Maria
AU  - Koffa M
AUID- ORCID: 0000-0003-2255-3426
AD  - Laboratory of Molecular Cell Biology, Department of Molecular Biology and 
      Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Arvanitidis, Konstantinos
AU  - Arvanitidis K
AUID- ORCID: 0000-0003-0639-2474
AD  - Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 
      Alexandroupolis, Greece.
FAU - Bamias, Giorgos
AU  - Bamias G
AUID- ORCID: 0000-0002-5492-5717
AD  - GI-Unit, Third Department of Internal Medicine, National & Kapodistrian 
      University of Athens, Sotiria Hospital, Athens, Greece.
FAU - Valatas, Vassilis
AU  - Valatas V
AUID- ORCID: 0000-0001-6660-0621
AD  - Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 
      Alexandroupolis, Greece.
AD  - Gastroenterology and Hepatology Research Laboratory, Medical School, University 
      of Crete, Heraklion, Greece.
FAU - Paspaliaris, Vasilis
AU  - Paspaliaris V
AUID- ORCID: 0000-0003-0274-3046
AD  - Tithon Biotech Inc., San Diego, USA.
FAU - Kolios, George
AU  - Kolios G
AUID- ORCID: 0000-0002-2066-4782
AD  - Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, 
      Alexandroupolis, Greece.
LA  - eng
PT  - Journal Article
DEP - 20210727
PL  - United States
TA  - Stem Cells Int
JT  - Stem cells international
JID - 101535822
PMC - PMC8331310
COIS- The authors have no conflict to declare.
EDAT- 2021/08/07 06:00
MHDA- 2021/08/07 06:01
PMCR- 2021/07/27
CRDT- 2021/08/06 06:50
PHST- 2021/03/04 00:00 [received]
PHST- 2021/06/08 00:00 [revised]
PHST- 2021/07/01 00:00 [accepted]
PHST- 2021/08/06 06:50 [entrez]
PHST- 2021/08/07 06:00 [pubmed]
PHST- 2021/08/07 06:01 [medline]
PHST- 2021/07/27 00:00 [pmc-release]
AID - 10.1155/2021/9929461 [doi]
PST - epublish
SO  - Stem Cells Int. 2021 Jul 27;2021:9929461. doi: 10.1155/2021/9929461. eCollection 
      2021.