Initial pig developmental stage influences intestinal organoid growth but not cellular composition

Abstract Background Intestinal organoids are promising tools in the context of animal experiment reduction but a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate th...

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Main Authors: Camille Duchesne, Gwénaëlle Randuineau, Laurence Le Normand, Véronique Romé, Samia Laraqui, Alexis Pierre Arnaud, Gaëlle Boudry
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Animal Models and Experimental Medicine
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Online Access:https://doi.org/10.1002/ame2.12512
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author Camille Duchesne
Gwénaëlle Randuineau
Laurence Le Normand
Véronique Romé
Samia Laraqui
Alexis Pierre Arnaud
Gaëlle Boudry
author_facet Camille Duchesne
Gwénaëlle Randuineau
Laurence Le Normand
Véronique Romé
Samia Laraqui
Alexis Pierre Arnaud
Gaëlle Boudry
author_sort Camille Duchesne
collection DOAJ
description Abstract Background Intestinal organoids are promising tools in the context of animal experiment reduction but a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate the effect of ISC donor age on the growth, morphology and cellular composition of intestinal organoids derived from pig. Methods Organoids were derived from jejunal and colonic ISC obtained from 1‐, 7‐, 28‐, 36‐ and 180‐day‐old pigs and passaged three times. Results We first confirmed by qPCR that the expression of 18% of the >80 studied genes related to various intestinal functions differed between jejunal and colonic organoids after two passages (p < 0.05). Growth and morphology of organoids depended on intestinal location (greater number and larger organoids derived from colonic than jejunal ISC, p < 0.05) but also pig age. Indeed, when ISC were derived from young piglets, the ratio of organoids to spheroids was greater (p < 0.05), spheroids were larger during the primary culture but smaller after two passages (p < 0.05) and organoids were smaller after one passage (p > 0.05) compared to ISC from older pigs. Finally, no difference in cellular composition, evaluated by immunostaining of markers of the major intestinal cell types (absorptive, enteroendocrine and goblet cells) was observed between organoids originating from 7‐ or 180‐day‐old pigs, but differences between intestinal site origins were noticed. Conclusion In conclusion, while the age of the tissue donor affected organoid growth and morphology, it did not influence the phenotype.
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spelling doaj-art-40d37611aa6845deb5073c00bbd875ca2025-08-20T02:01:24ZengWileyAnimal Models and Experimental Medicine2576-20952024-12-017694495410.1002/ame2.12512Initial pig developmental stage influences intestinal organoid growth but not cellular compositionCamille Duchesne0Gwénaëlle Randuineau1Laurence Le Normand2Véronique Romé3Samia Laraqui4Alexis Pierre Arnaud5Gaëlle Boudry6Institut Numecan, INRAE, INSERM Univ Rennes Rennes FranceInstitut Numecan, INRAE, INSERM Univ Rennes Rennes FranceInstitut Numecan, INRAE, INSERM Univ Rennes Rennes FranceInstitut Numecan, INRAE, INSERM Univ Rennes Rennes FranceInstitut Numecan, INRAE, INSERM Univ Rennes Rennes FranceInstitut Numecan, INRAE, INSERM Univ Rennes Rennes FranceInstitut Numecan, INRAE, INSERM Univ Rennes Rennes FranceAbstract Background Intestinal organoids are promising tools in the context of animal experiment reduction but a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate the effect of ISC donor age on the growth, morphology and cellular composition of intestinal organoids derived from pig. Methods Organoids were derived from jejunal and colonic ISC obtained from 1‐, 7‐, 28‐, 36‐ and 180‐day‐old pigs and passaged three times. Results We first confirmed by qPCR that the expression of 18% of the >80 studied genes related to various intestinal functions differed between jejunal and colonic organoids after two passages (p < 0.05). Growth and morphology of organoids depended on intestinal location (greater number and larger organoids derived from colonic than jejunal ISC, p < 0.05) but also pig age. Indeed, when ISC were derived from young piglets, the ratio of organoids to spheroids was greater (p < 0.05), spheroids were larger during the primary culture but smaller after two passages (p < 0.05) and organoids were smaller after one passage (p > 0.05) compared to ISC from older pigs. Finally, no difference in cellular composition, evaluated by immunostaining of markers of the major intestinal cell types (absorptive, enteroendocrine and goblet cells) was observed between organoids originating from 7‐ or 180‐day‐old pigs, but differences between intestinal site origins were noticed. Conclusion In conclusion, while the age of the tissue donor affected organoid growth and morphology, it did not influence the phenotype.https://doi.org/10.1002/ame2.12512colonoiddevelopmententeroidorganoid phenotypepiglet
spellingShingle Camille Duchesne
Gwénaëlle Randuineau
Laurence Le Normand
Véronique Romé
Samia Laraqui
Alexis Pierre Arnaud
Gaëlle Boudry
Initial pig developmental stage influences intestinal organoid growth but not cellular composition
Animal Models and Experimental Medicine
colonoid
development
enteroid
organoid phenotype
piglet
title Initial pig developmental stage influences intestinal organoid growth but not cellular composition
title_full Initial pig developmental stage influences intestinal organoid growth but not cellular composition
title_fullStr Initial pig developmental stage influences intestinal organoid growth but not cellular composition
title_full_unstemmed Initial pig developmental stage influences intestinal organoid growth but not cellular composition
title_short Initial pig developmental stage influences intestinal organoid growth but not cellular composition
title_sort initial pig developmental stage influences intestinal organoid growth but not cellular composition
topic colonoid
development
enteroid
organoid phenotype
piglet
url https://doi.org/10.1002/ame2.12512
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