Evaluation of transplantation sites for human intestinal organoids.

Our group has developed two transplantation models for the engraftment of Human Intestinal Organoids (HIOs): the renal subcapsular space (RSS) and the mesentery each with specific benefits for study. While engraftment at both sites generates laminated intestinal structures, a direct comparison betwe...

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Main Authors: Akaljot Singh, Holly M Poling, Nambirajan Sundaram, Nicole Brown, James M Wells, Michael A Helmrath
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0237885
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author Akaljot Singh
Holly M Poling
Nambirajan Sundaram
Nicole Brown
James M Wells
Michael A Helmrath
author_facet Akaljot Singh
Holly M Poling
Nambirajan Sundaram
Nicole Brown
James M Wells
Michael A Helmrath
author_sort Akaljot Singh
collection DOAJ
description Our group has developed two transplantation models for the engraftment of Human Intestinal Organoids (HIOs): the renal subcapsular space (RSS) and the mesentery each with specific benefits for study. While engraftment at both sites generates laminated intestinal structures, a direct comparison between models has not yet been performed. Embryonic stem cells were differentiated into HIOs, as previously described. HIOs from the same batch were transplanted on the same day into either the RSS or mesentery. 10 weeks were allowed for engraftment and differentiation, at which time they were harvested and assessed. Metrics for comparison included: mortality, engraftment rate, gross size, number and grade of lumens, and expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism. Mortality was significantly increased when undergoing mesentery transplantation, however engraftment was significantly higher. Graft sizes were similar between groups. Morphometric parameters were similar between groups, however m-tHIOs presented with significantly fewer lumens than k-tHIO. Transcript and protein level expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism were similar between groups. Transplantation into both sites yields viable tissue of similar quality based on our assessments with enhanced engraftment and a dominant lumen for uniform study benefiting the mesenteric site and survival benefiting RSS.
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spelling doaj.art-4df5319f91e4406ea55d08281fbc74422023-06-05T05:32:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01158e023788510.1371/journal.pone.0237885Evaluation of transplantation sites for human intestinal organoids.Akaljot SinghHolly M PolingNambirajan SundaramNicole BrownJames M WellsMichael A HelmrathOur group has developed two transplantation models for the engraftment of Human Intestinal Organoids (HIOs): the renal subcapsular space (RSS) and the mesentery each with specific benefits for study. While engraftment at both sites generates laminated intestinal structures, a direct comparison between models has not yet been performed. Embryonic stem cells were differentiated into HIOs, as previously described. HIOs from the same batch were transplanted on the same day into either the RSS or mesentery. 10 weeks were allowed for engraftment and differentiation, at which time they were harvested and assessed. Metrics for comparison included: mortality, engraftment rate, gross size, number and grade of lumens, and expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism. Mortality was significantly increased when undergoing mesentery transplantation, however engraftment was significantly higher. Graft sizes were similar between groups. Morphometric parameters were similar between groups, however m-tHIOs presented with significantly fewer lumens than k-tHIO. Transcript and protein level expression of markers specific to epithelial differentiation, mesenchymal differentiation, and carbohydrate metabolism were similar between groups. Transplantation into both sites yields viable tissue of similar quality based on our assessments with enhanced engraftment and a dominant lumen for uniform study benefiting the mesenteric site and survival benefiting RSS.https://doi.org/10.1371/journal.pone.0237885
spellingShingle Akaljot Singh
Holly M Poling
Nambirajan Sundaram
Nicole Brown
James M Wells
Michael A Helmrath
Evaluation of transplantation sites for human intestinal organoids.
PLoS ONE
title Evaluation of transplantation sites for human intestinal organoids.
title_full Evaluation of transplantation sites for human intestinal organoids.
title_fullStr Evaluation of transplantation sites for human intestinal organoids.
title_full_unstemmed Evaluation of transplantation sites for human intestinal organoids.
title_short Evaluation of transplantation sites for human intestinal organoids.
title_sort evaluation of transplantation sites for human intestinal organoids
url https://doi.org/10.1371/journal.pone.0237885
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