Faculty, Staff and Student Publications
Publication Date
12-1-2022
Journal
Digestive Diseases and Sciences
Abstract
Background: Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed.
Aims: We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development.
Methods: HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8-9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR performed. Morphology was evaluated and epithelial architecture graded on a scale of 1 (absence of crypts/villi) to 4 (elongated crypt-villus axis). RT-qPCR and immunofluorescence microscopy were performed for epithelial and mesenchymal differentiation markers.
Results: Host survival and tHIO engraftment were equivalent in male and female hosts. tHIO weight and length were also equivalent between groups. The number of lumens per tHIOs from male and female hosts was similar, but the mean lumen circumference was larger for tHIOs from male hosts. tHIOs from male hosts were more likely to demonstrate higher grades of epithelial development. However, both groups showed similar differentiation into secretory and absorptive epithelial lineages. Markers for intestinal identity, mesenchymal development, and brush border enzymes were also expressed similarly between groups.
Conclusions: While male host sex was associated with larger tHIO lumen size and mucosal maturation, tHIOs from both groups had similar engraftment, growth, and epithelial and mesenchymal cytodifferentiation.
Keywords
Humans, Male, Female, Mice, Animals, Organoids, Intestines, Intestinal Mucosa, Microvilli, Transplants, Human intestinal organoid, Organoid, Sex-related differences, Sex as a biological variable, Intestinal failure, Short bowel syndrome
DOI
10.1007/s10620-022-07442-7
PMID
35334015
PMCID
PMC10251489
PubMedCentral® Posted Date
12-1-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Digestive System Diseases Commons, Gastroenterology Commons, Medical Sciences Commons, Pediatrics Commons, Surgery Commons