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Cited by 127Gastrointestinal motility and disordersCongenital gastrointestinal and neural anomaliesGastrointestinal Tumor Research and Treatment

The DOI matches its Crossref record; 110 of the 112 references it cites were found in a registry or an index.

Understanding the Biology of Human Interstitial Cells of Cajal in Gastrointestinal Motility

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Foong, Daphne, Zhou, Jerry, Zarrouk, Ali, Ho, Vincent, O’Connor, Michael D.·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21124540PMC PMC7352366
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Abstract

Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility.

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Crossref · 10.3390/ijms21124540

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Figures

Figure 1 Identification and capture of candidate interstitial cells of Cajal (ICC) from human gastric muscle tissue. (A) Outline of the experimental workflow for processing human sleeve gastrectomy samples for immunofluorescence or flow cytometry. (B–E) Immunofluorescence data obtained from cryosections of human gastric muscle stained with DAPI nuclear stain (blue) and antibodies that detect ICC marker proteins ANO1 (B; green) and KIT (C; red), with overlapping expression observed (D; ANO1+KIT+DAPI). A representative negative control (E; secondary antibody only control+DAPI) shows no background staining, thereby supporting the specificity of the staining patterns seen in B–D. Images were taken at 40× objective on the Zeiss Axio Imager M2 microscope. Scale bar = 50 μm. (F) A representative fluorescence-activated cell sorting (FACS) plot illustrating key human sleeve gastrectomy cell populations including: KIT+/CD45-/CD11b- ICC (red box); hematopoietic cells (HP; KIT-/CD45+/CD11b+) (grey box); and mast cells (MC; KIT+/CD45+/CD11b+) (grey box). (G) Plot of ICC frequency and total sorted ICC numbers. Each dot represents an individual patient sample. (H) RT-PCR verification of cell marker genes in the FACS-captured ICC population: ANO1 (ICC), KIT (ICC, mast cells), CPA3 (mast cells), and CD68 (hematopoietic cells). Data were normalised against GAPDH mRNA levels, expressed relative to unsorted cells (dotted line), and represented as mean fold change ± standard error of the mean from three biological samples. Data were analysed using paired t-test; * p < 0.05, ** p < 0.01.
Figure 1 Identification and capture of candidate interstitial cells of Cajal (ICC) from human gastric muscle tissue. (A) Outline of the experimental workflow for processing human sleeve gastrectomy samples for immunofluorescence or flow cytometry. (B–E) Immunofluorescence data obtained from cryosections of human gastric muscle stained with DAPI nuclear stain (blue) and antibodies that detect ICC marker proteins ANO1 (B; green) and KIT (C; red), with overlapping expression observed (D; ANO1+KIT+DAPI). A representative negative control (E; secondary antibody only control+DAPI) shows no background staining, thereby supporting the specificity of the staining patterns seen in B–D. Images were taken at 40× objective on the Zeiss Axio Imager M2 microscope. Scale bar = 50 μm. (F) A representative fluorescence-activated cell sorting (FACS) plot illustrating key human sleeve gastrectomy cell populations including: KIT+/CD45-/CD11b- ICC (red box); hematopoietic cells (HP; KIT-/CD45+/CD11b+) (grey box); and mast cells (MC; KIT+/CD45+/CD11b+) (grey box). (G) Plot of ICC frequency and total sorted ICC numbers. Each dot represents an individual patient sample. (H) RT-PCR verification of cell marker genes in the FACS-captured ICC population: ANO1 (ICC), KIT (ICC, mast cells), CPA3 (mast cells), and CD68 (hematopoietic cells). Data were normalised against GAPDH mRNA levels, expressed relative to unsorted cells (dotted line), and represented as mean fold change ± standard error of the mean from three biological samples. Data were analysed using paired t-test; * p < 0.05, ** p < 0.01.CC BY · PubMed Central
Figure 2 Workflow for characterisation of patient-derived human gastric interstitial cells of Cajal (ICC).
Figure 2 Workflow for characterisation of patient-derived human gastric interstitial cells of Cajal (ICC).CC BY · PubMed Central

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Citations

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Research works printed but not linked: 2

  1. Cajal, 1911, Histologie du syste me nerveux de I’Homme et des verte be s, Maloine (Paris), 2, 891
  2. Komuro, 1999, Comparative morphology of interstitial cells of Cajal: Ultrastructural characterization, Microsc. Res. Tech., 47, 267, 10.1002/(SICI)1097-0029(19991115)47:4<267::AID-JEMT5>3.0.CO;2-O · DOI

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Metadata

Authors
Foong, D., Zhou, J., Zarrouk, A., Ho, V., & O’Connor, M. D.
Affiliations
  • Western Sydney University (AU)
  • Campbelltown Private Hospital, Campbelltown, NSW 2560, Australia
Corresponding author
O’Connor, Michael D.
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-06-25
Volume
21
Issue
12
Pages
4540
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21124540
PMC
PMC7352366
OpenAlex
W3037610538
Cited by
127
References
112
Citations by year
2026: 14 · 2025: 30 · 2024: 30 · 2023: 22 · 2022: 20 · 2021: 10 · 2020: 1
FWCI
2.30
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • University of Western Sydney (N/A)
  • Australian Rotary Health (N/A)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal Tumor Research and Treatment
Keywords
interstitial cells of Cajal, gastrointestinal motility, gastroparesis, peristalsis, slow waves, gastric smooth muscle, primary human cells, gastrointestinal motility disorders, therapeutic target
MeSH terms
Gastrointestinal Diseases, Gastrointestinal Motility, Humans, Intestine, Small, Peristalsis, Stomach, Myocytes, Smooth Muscle, Gastrointestinal Tract, Interstitial Cells of Cajal

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