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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
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Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
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Rectal Epithelial Stem Cell Kinetics in Acute Radiation Proctitis.

Sharmila Ghosh1, Akinori Morita1, Yuichi Nishiyama1

  • 1Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan.

International Journal of Molecular Sciences
|October 26, 2024
PubMed
Summary
This summary is machine-generated.

Radiation rectal injury impacts radiotherapy. Lgr5-positive stem cells show distinct patterns after irradiation, with a threshold dose of 18 Gy for structural destruction, aiding understanding of intestinal injury.

Keywords:
Lgr5-positive stem cellcaudal half-body irradiationcrypt base regenerationmouse modelradiation proctitis

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Area of Science:

  • Gastroenterology
  • Radiation Oncology
  • Stem Cell Biology

Background:

  • Radiation rectal injury is a significant side effect limiting radiotherapy doses in abdominal and pelvic regions.
  • Understanding the behavior of Lgr5-positive stem cells post-irradiation is key to comprehending rectal injury.
  • Lgr5 is a marker for stem cells in various tissues, including the intestinal tract.

Purpose of the Study:

  • To investigate the post-irradiation kinetics of Lgr5-positive stem cells in rectal tissue.
  • To analyze the dose-response relationship of Lgr5 expression and stem cell distribution after radiation exposure.
  • To determine the threshold radiation dose that destroys Lgr5-positive stem cell structures.

Main Methods:

  • Utilized Lgr5-EGFP knock-in mice and LGR5 antibody fluorescence staining in wild-type mice.
  • Performed qPCR analysis to assess Lgr5 expression levels in rectal epithelial tissue.
  • Conducted dose-response relationship analysis and statistical analysis to identify the threshold dose.

Main Results:

  • Radiation injury significantly decreased Lgr5 expression in rectal epithelial tissue.
  • Low to moderate doses (up to 10 Gy) showed clustered Lgr5 populations, while sublethal doses (20-29 Gy) resulted in scattered 'Lgr5-dotted' populations.
  • A threshold dose of 18 Gy was identified for the destruction of Lgr5-positive stem cell structures.
  • During recovery, clustered Lgr5 populations re-emerged, and dotted populations declined, suggesting regeneration.

Conclusions:

  • Lgr5-positive stem cell behavior changes dynamically with radiation dose and recovery time.
  • The identified threshold dose of 18 Gy is critical for understanding radiation-induced intestinal injury in experimental models.
  • These findings contribute to optimizing radiation doses in mouse models and elucidating the histological processes of radiation injury.