Bridging the gap: functional healing of embryonic small intestine ex vivo.
Bridging the gap: functional healing of embryonic small intestine ex vivo.
复制标题
DOI：
10.1002/term.2073
复制
发表时间：
2016-02
影响因子：
3.3
通讯作者：
Woolf AS
中科院分区：
文献类型：
--
作者：
Coletta R;Roberts NA;Oltrabella F;Khalil BA;Morabito A;Woolf AS
离体培养胚胎器官的能力提供了在受控环境中跟踪其分化的机会，从而了解正常发育。此外，类似的策略可用于评估物理和化学操作对器官发生的影响。本研究旨在建立一个器官培养模型，以测试物理操作，以加强愈合的肠段，从而产生一个单一的功能器官。分离胚胎小鼠空肠并切成2-3 mm管，将其成对放置在半渗透性支持物上，以小间隙隔开。每一对都由穿过它们管腔的尼龙缝线连接。在由确定的无血清培养基喂养的器官培养物中3天后，雏形分化形成围绕雏形绒毛核心的平滑肌管。在34个这样的对中，74%的近端接触且对齐良好。在这些连接的结构中，80%（总对的59%）具有连续的管腔，如通过观察注射到其远端的荧光葡聚糖的轨迹所评估的。融合的器官对形成一个单一的功能单位，如通过自发收缩波沿其长度传播沿着评估。在这些愈合的肠道中，外周蛋白+神经元在融合区形成了一个连接，连接了雏形对。将来，这个系统可以用来测试生长因子是否能增强融合。这样的结果反过来应该为短肠综合征的新治疗方法的设计提供信息，短肠综合征是一种潜在的致命疾病，目前治疗范围有限且不完善。©2015年。作者组织工程和再生医学杂志出版的约翰威利父子公司，有限公司
The ability to grow embryonic organs ex vivo provides an opportunity to follow their differentiation in a controlled environment, with resulting insights into normal development. Additionally, similar strategies can be used to assess effects on organogenesis of physical and chemical manipulations. This study aimed to create an organ culture model with which to test physical manipulations to enhance healing of gut segments, thus generating a single functional organ. Embryonic mouse jejunum was isolated and cut into 2–3 mm tubes, which were placed in pairs, separated by a small gap, on semi‐permeable supports. Each pair was linked by a nylon suture threaded through their lumens. After 3 days in organ culture fed by defined serum‐free media, the rudiments differentiated to form tubes of smooth muscle surrounding a core of rudimentary villi. Of 34 such pairs, 74% had touching and well aligned proximate ends. Of these joined structures, 80% (59% of the total pairs) had a continuous lumen, as assessed by observing the trajectories of fluorescent dextrans injected into their distal ends. Fused organ pairs formed a single functional unit, as assessed by spontaneous contraction waves propagated along their lengths. In these healed intestines, peripherin+ neurons formed a nexus in the zone of fusion, linking the rudiment pairs. In future, this system could be used to test whether growth factors enhance fusion. Such results should in turn inform the design of novel treatments for short bowel syndrome, a potentially fatal condition with a currently limited and imperfect range of therapies. ©2015. The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons, Ltd