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

Purpose Preterm infants are more susceptible to necrotizing enterocolitis (NEC) than term Queryinfants. This may be due to a relative paucity of Lgr5 + or Bmi1 + -expressing intestinal stem cells (ISCs) which are responsible for promoting intestinal recovery after injury. We hypothesized that the cellular markers of Lgr5 + and Bmi1 + , which represent the two distinct ISC populations, would be lower in younger mice compared to older mice. In addition, we hypothesized that experimental NEC would result in a greater loss of Lgr5 + expression compared to Bmi1 + expression. Methods Transgenic mice with EGFP-labeled Lgr5 underwent euthanasia at 10 different time points from E15 to P56 ( n = 8–11/group). Lgr5 + -expressing ISCs were quantified by GFP ELISA and Bmi1 + was assessed by qPCR. In addition, Lgr5 EGFP mice underwent experimental NEC via formula feeding and hypoxic and hypothermic stress. Additional portions of the intestine underwent immunostaining with anti-GFP or anti- Bmi1 + antibodies to confirm ELISA and PCR results. For statistical analysis, p < 0.05 was significant. Results Lgr5 + and Bmi1 + expression was lowest in embryonal and early postnatal mice and increased with age in all segments of the intestine. Experimental NEC was associated with loss of Lgr5 + -expressing ISCs but no significant change in Bmi1 + expression. Conclusion Lgr5 + and Bmi1 + expression increase with age. Lgr5 + -expressing ISCs are lower following experimental necrotizing enterocolitis while Bmi1 + expression remains relatively unchanged. Developing a targeted medical therapy to protect the low population of ISCs in preterm infants may promote tissue recovery and regeneration after injury from NEC.