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08.10.2022 | Original Article

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

verfasst von: Brian D. Hosfield, W. Christopher Shelley, Fikir M. Mesfin, John P. Brokaw, Krishna Manohar, Jianyun Liu, Hongge Li, Anthony R. Pecoraro, Kanhaiya Singh, Troy A. Markel

Erschienen in: Pediatric Surgery International | Ausgabe 12/2022

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Abstract

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.

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Titel: Age disparities in intestinal stem cell quantities: a possible explanation for preterm infant susceptibility to necrotizing enterocolitis
verfasst von: Brian D. Hosfield
W. Christopher Shelley
Fikir M. Mesfin
John P. Brokaw
Krishna Manohar
Jianyun Liu
Hongge Li
Anthony R. Pecoraro
Kanhaiya Singh
Troy A. Markel
Publikationsdatum: 08.10.2022
Verlag: Springer Berlin Heidelberg
Erschienen in: Pediatric Surgery International / Ausgabe 12/2022
Print ISSN: 0179-0358
Elektronische ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-022-05257-1

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