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 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 Bmi1expression 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.