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.
J Tissue Eng Regen Med. 2018 Jan;12(1):252-264. doi: 10.1002/term.2409. Epub 2017 Apr 27.
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.
一种能够模拟体内肠道发育的离体实验策略,从理论上讲,为研究正常和畸形肠道生物学提供了一种可接近的环境。作者最近描述了一种系统,其中将小鼠胚胎空肠段置于半透性平台上,并使用化学定义的无血清培养基进行喂养。在器官培养中,离体培养物在 3 天内形成绒毛,并且开始自发蠕动。如本研究中所定义的,离体肠道壁未能形成像在体内相同时间内那样强健的纵向平滑肌(SM)层。鉴于转化生长因子β 1(TGFβ1)在其他器官中的 SM 分化中的作用,假设外源性 TGFβ1 将增强这些离体培养物中的 SM 分化。在体内,TGFβ 受体 I 和 II 均在胚胎纵向空肠 SM 细胞中被检测到,在器官培养中,外源性 TGFβ1 诱导纵向 SM 的强烈分化。微阵列分析显示,TGFβ1 以剂量依赖的方式增加 SM 特异性转录物。在肠生理疝出时,在羊水中检测到 TGFβ1 蛋白。与器官培养中 SM 分化需要外源性 TGFβ1 相似,证明在羊水存在的 TGFβ1 蛋白可能在早期妊娠中肠生理疝出时增强肠道发育。未来对胚胎肠培养物的研究应在定义的培养基中包含 TGFβ1,以产生更真实的体内肌肉分化模型。版权所有©2017 作者 组织工程与再生医学杂志 由 John Wiley & Sons,Ltd. 出版