Fetal tissue engineering: Diaphragmatic replacement

Fetal tissue engineering: Diaphragmatic replacement
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DOI:
10.1053/jpsu.2001.20034
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发表时间:
2001-01-01
影响因子:
2.4
通讯作者:
Vacanti, JP
Vacanti, JP
中科院分区:
医学3区
文献类型:
--
作者:
Fauza, DO;Marler, JJ;Vacanti, JP

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背景/目的:先天性膈疝的假体修复与高并发症发生率相关。本研究旨在将胎儿组织工程应用于膈肌置换术。方法:采集胎羊骨骼肌标本。一旦在体外扩增,胎儿成肌细胞就会悬浮在胶原水凝胶中,并受到受控的径向张力。然后将该构建体放入生物反应器中。出生后,所有动物均出现 2 处膈肌缺陷。一个缺陷是用放置在两个无细胞支撑膜之间的自体工程构建体修复的,另一个缺陷是用相同的构建体修复的,但没有任何细胞。每只动物都有自己的对照(移植物,n = 10)。在植入后的不同时间点处死动物以进行组织学检查。通过方差分析(ANOVA)进行统计分析。结果:胎儿成肌细胞的扩增速度是新生儿细胞的两倍。基于水凝胶的径向张力通过引发支架内的细胞组织来增强构建结构。 5 个工程构建体中有 4 个不存在事件发生,但 5 个无细胞移植物中有 0 个不存在事件发生 (P < .05)。收获时,工程化构建体较厚,组织学上类似于正常骨骼肌,而无细胞移植物较薄、松软,细胞密度低,纤维化增加。结论:与无细胞移植物不同,工程化细胞膈肌构建体在解剖学和组织学上与正常肌肉相似。胎儿组织工程可能是膈肌置换术的可行替代方案。小儿外科杂志 36:146-151。版权所有 (C) 2001 W.B.桑德斯公司。
Background/Purpose: Prosthetic repair of congenital diaphragmatic hernia has been associated with high complication rates. This study was aimed at applying fetal tissue engineering to diaphragmatic replacement.Methods: Fetal lambs underwent harvest of skeletal muscle specimens. Once expanded in vitro, fetal myoblasts were suspended in a collagen hydrogel submitted to controlled radial tension. The construct was then placed in a bioreactor. After birth, all animals underwent creation of 2 diaphragmatic defects. One defect was repaired with the autologous-engineered construct placed in between 2 acellular supporting membranes and the other with an identical construct but without any cells. Each animal was its own control (graft, n = 10). Animals were killed at different time-points postimplantation for histologic examination. Statistical analysis was by analysis of variance (ANOVA).Results: Fetal myoblasts expanded up to twice as fast as neonatal cells. Hydrogel-based radial tension enhanced construct architecture by eliciting cell organization within the scaffold. No eventration was present in 4 of 5 engineered constructs but in 0 of 5 acellular grafts (P < .05). At harvest, engineered constructs were thick and histologically resembled normal skeletal muscle, whereas acellular grafts were thin, floppy, and showed low cell density with increased fibrosis.Conclusions: Unlike acellular grafts, engineered cellular diaphragmatic constructs are anatomically and histologically similar to normal muscle. Fetal tissue engineering may be a viable alternative for diaphragmatic replacement. J Pediatr Surg 36:146-151. Copyright (C) 2001 by W.B. Saunders Company.