Allo- and xeno-reassembly of human and rat myometrium from cells and scaffolds.
Allo- and xeno-reassembly of human and rat myometrium from cells and scaffolds.
复制标题
从细胞和支架对人和大鼠子宫肌层进行同种异体和异种重组。
DOI：
10.1089/ten.tea.2012.0549
复制
发表时间：
2013
影响因子：
--
通讯作者：
Goloman,Gabriela
中科院分区：
文献类型：
--
作者：
Young,RogerC;Goloman,Gabriela
将分离的肌细胞培养成去细胞化的大鼠和人肌层支架，形成新肌层。子宫的双重作用是容纳生长中的胎儿，然后在足月时通过阶段性收缩将胎儿排出体外。第一个功能需要物理健壮性以及扩展和改造的能力。先天性异常或以前的手术会机械地损害子宫，导致妊娠期的主要并发症。第二个功能利用了复杂生理机制的多种相互作用，但尚未完全阐明，这种知识差距有助于妊娠严重并发症的持续。为了解决这两个问题，我们用分离的肌细胞和支架重建了肌层。从大鼠和人的肌层中，用胶原酶消化分离肌细胞，用乙醇/胰蛋白酶分离支架。采用单层培养扩增肌细胞数量，再将肌细胞培养回支架内。我们称这种工程组织为新肌层，同种新肌层由同一物种的成分制成，异种新肌层由不同物种的成分制成。通过人工制造大鼠支架缺损，制备出异体-新肌层，并表现出支架的快速重构。构建了Xeno-neo myometrium（人肌细胞/大鼠支架），并在支架中发现肌细胞呈500 μm深的束状分布。这些实验提供了原理证明，适量的肌细胞可以被扩增并用于创建更大体积的工程组织，这可能对半自体移植修复人类子宫的结构缺陷有用。在等长收缩实验中，异种新肌层（人肌细胞，大鼠支架）观察到协调收缩，而异种新肌层（人肌细胞，人支架）没有观察到协调收缩。
Neo-myometrium was created by culturing isolated myocytes into decellularized rat and human myometrial scaffolds. The dual purpose of the uterus is to accommodate the growing fetus, and then expel the fetus at term by phasically contracting it. The first function requires physical robustness as well as the ability to expand and remodel. Congenital anomalies or previous surgeries can mechanically compromise the uterus and lead to major complications in pregnancy. The second function utilizes multiple interactions of complex physiological mechanisms that have yet to be fully elucidated, and this knowledge gap contributes to the continuation of serious complications of pregnancy. To address both problems, we reconstructed myometrium from isolated myocytes and scaffold. From both rat and human myometrium, myocytes were isolated using collagenase digestion, and scaffolds were isolated using ethanol/ trypsin protocols. The number of myocytes was amplified using monolayer culture, and then, the myocytes were cultured back into the scaffolds. We called this engineered tissue neo-myometrium, with allo-neo-myometrium being made from components of the same species, and xeno-neo-myometrium from across species. By artificially creating defects in rat scaffold, allo-neo-myometrium was created that demonstrated rapid scaffold remodeling. Xeno-neo myometrium (human myocytes/rat scaffold) was created and demonstrated myocytes occurring in bundles 500 μm deep in the scaffold. These experiments provide proof of principle that modest numbers of myocytes can be amplified and used to create a larger volume of engineered tissue, which may be useful for semi-autologous transplantation to repair structural defects of the human uterus. In isometric contractility experiments, coordinated contractions were observed in xeno-neo-myometrium (human myocytes, rat scaffold), but not allo-neo-myometrium (human myocytes, human scaffold).