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Age disparities in intestinal stem cell quantities: a possible explanation for preterm infant susceptibility to

Brian D Hosfield1, W Christopher Shelley1, Fikir M Mesfin1

  • 1Department of Surgery, Section of Pediatric Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.

Pediatric Surgery International
|October 8, 2022
PubMed

Insights

Preterm infants have fewer intestinal stem cells (ISCs), making them vulnerable to necrotizing enterocolitis (NEC). This study found Lgr5+ ISCs decrease with NEC, suggesting a therapeutic target for infant gut injury.

Area of Science:

  • Gastroenterology
  • Developmental Biology
  • Stem Cell Biology

Background:

  • Preterm infants are at higher risk for necrotizing enterocolitis (NEC) compared to full-term infants.
  • This increased susceptibility may be linked to a lower number of intestinal stem cells (ISCs), specifically Lgr5+ and Bmi1+ expressing cells, which are crucial for intestinal repair.
  • Understanding the dynamics of these ISC populations in relation to age and NEC is vital for developing effective treatments.

Purpose of the Study:

  • To investigate the age-dependent expression of Lgr5+ and Bmi1+ intestinal stem cells (ISCs) in mice.
  • To determine the impact of experimental necrotizing enterocolitis (NEC) on Lgr5+ and Bmi1+ ISC populations.
  • To test the hypothesis that younger mice have lower ISC markers and that NEC disproportionately affects Lgr5+ ISCs.

Main Methods:

  • Utilized transgenic mice with EGFP-labeled Lgr5 and assessed Bmi1+ expression via qPCR.
  • Quantified Lgr5+ ISCs using GFP ELISA across 10 developmental time points (E15-P56).
  • Induced experimental NEC in Lgr5EGFP mice through formula feeding, hypoxia, and hypothermia, followed by immunostaining and statistical analysis.

Main Results:

  • Both Lgr5+ and Bmi1+ expression levels were lowest in embryonic and early postnatal mice, increasing with age.
  • Experimental NEC led to a significant reduction in Lgr5+-expressing ISCs.
  • No significant change in Bmi1+ expression was observed following experimental NEC.

Conclusions:

  • Intestinal stem cell markers Lgr5+ and Bmi1+ expression increase with age in mice.
  • Lgr5+ ISCs are diminished following experimental NEC, while Bmi1+ expression remains stable.
  • Targeting therapies to protect the limited ISC population in preterm infants could enhance recovery from NEC-induced intestinal injury.
Abstract

Keywords:
Animal studyBmi1Intestinal stem cellsLgr5Necrotizing enterocolitis

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