title: Exogenous transforming growth factor-β1 enhances smooth muscle differentiation in embryonic mouse jejunal explants.
abstract: An ex vivo experimental strategy that replicates in vivo intestinal development would in theory provide an accessible setting with which to study normal and dysmorphic gut biology. The current authors recently described a system in which mouse embryonic jejunal segments were explanted onto semipermeable platforms and fed with chemically defined serum-free media. Over 3 days in organ culture, explants formed villi and they began to undergo spontaneous peristalsis. As defined in the current study, the wall of the explanted gut failed to form a robust longitudinal smooth muscle (SM) layer as it would do in vivo over the same time period. Given the role of transforming growth factor β1 (TGFβ1) in SM differentiation in other organs, it was hypothesized that exogenous TGFβ1 would enhance SM differentiation in these explants. In vivo, TGFβ receptors I and II were both detected in embryonic longitudinal jejunal SM cells and, in organ culture, exogenous TGFβ1 induced robust differentiation of longitudinal SM. Microarray profiling showed that TGFβ1 increased SM specific transcripts in a dose dependent manner. TGFβ1 proteins were detected in amniotic fluid at a time when the intestine was physiologically herniated. By analogy with the requirement for exogenous TGFβ1 for SM differentiation in organ culture, the TGFβ1 protein that was demonstrated to be present in the amniotic fluid may enhance intestinal development when it is physiologically herniated in early gestation. Future studies of embryonic intestinal cultures should include TGFβ1 in the defined media to produce a more faithful model of in vivo muscle differentiation. Copyright © 2017 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons, Ltd.
authors.affiliation: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK.|Paediatric Autologous Bowel Reconstruction and Rehabilitation Unit, Department of Paediatric Surgery, Royal Manchester Children's Hospital, Central Manchester Foundation Trust, Manchester, UK.
authors.forename: Riccardo
authors.identifier: 0000-0003-3878-1415
authors.initials: R
authors.lastname: Coletta
authors.affiliation: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Roberts
authors.affiliation: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK.|Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Randles
authors.affiliation: Paediatric Autologous Bowel Reconstruction and Rehabilitation Unit, Department of Paediatric Surgery, Royal Manchester Children's Hospital, Central Manchester Foundation Trust, Manchester, UK.|Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Antonino
authors.initials: A
authors.lastname: Morabito
authors.affiliation: Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, UK.|Department of Paediatric Nephrology, Royal Manchester Children's Hospital, Central Manchester Foundation Trust, Manchester, UK.
authors.forename: Adrian S
authors.identifier: 0000-0001-5541-1358
authors.initials: AS
authors.lastname: Woolf
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects; D006801:Humans; D007583:Jejunum / Q000196:embryology*; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1
keywords: culture; intestine; longitudinal; mesenchyme; microarray; organ