Feng Christina, Graham Christopher D, Connors John Patrick, Brazzo Joseph, Pan Amy H S, Hamilton James R, Zurakowski David, Fauza Dario O
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA.
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA.
J Pediatr Surg. 2016 Jan;51(1):56-61. doi: 10.1016/j.jpedsurg.2015.10.011. Epub 2015 Oct 22.
We sought to determine whether intraamniotic delivery of concentrated amniotic-derived mesenchymal stem cells (afMSCs) could reduce damage to exposed bowel in experimental gastroschisis.
Rat fetuses (n=117) with surgically created gastroschisis were divided into three groups: untreated animals (n=62) and two groups receiving volume-matched intraamniotic injections of either saline (n=25) or 2 × 10(6) cells/mL of syngeneic, labeled afMSCs (n=30). Animals were killed before term, along with normal controls (NL). Blinded observers performed computerized measurements of total and segmental (serosa, muscularis, and mucosa) intestinal wall thicknesses. Statistical comparisons were by ANOVA (P<0.05).
Among survivors with gastroschisis, there were statistically significant decreases in total bowel wall, serosal, muscular, and mucosal thicknesses in the afMSC group vs. the untreated group (P=0.001/0.035/0.001/0.005, respectively) and vs. the saline group (P=0.003/0.05/<0.001/0.026, respectively). There were no such significant differences between the untreated and saline groups. There were no differences between the afMSC group and NL, except for a significantly thicker muscular layer in the afMSC group (P=0.014). Labeled afMSCs were scarcely identified, suggesting a paracrine effect.
Amniotic mesenchymal stem cells mitigate bowel damage in experimental gastroschisis after concentrated intraamniotic injection. Transamniotic stem cell therapy (TRASCET) may become a practical component of the treatment of gastroschisis.
我们试图确定羊膜内注射浓缩的羊膜间充质干细胞（afMSCs）是否能减少实验性腹裂中暴露肠管的损伤。
通过手术制造腹裂的大鼠胎儿（n = 117）分为三组：未处理动物组（n = 62）以及另外两组，分别接受等体积羊膜内注射生理盐水（n = 25）或2×10⁶个细胞/毫升的同基因、标记的afMSCs（n = 30）。动物在足月前处死，同时处死正常对照（NL）。不知情的观察者对肠壁总厚度和各节段（浆膜、肌层和黏膜）厚度进行计算机测量。采用方差分析进行统计学比较（P < 0.05）。
在腹裂存活者中，afMSC组与未处理组相比，肠壁总厚度、浆膜、肌层和黏膜厚度均有统计学显著降低（分别为P = 0.001/0.035/0.001/0.005），与生理盐水组相比也有显著降低（分别为P = 0.003/0.05/<0.001/0.026）。未处理组和生理盐水组之间无此类显著差异。afMSC组与NL组之间无差异，但afMSC组的肌层明显更厚（P = 0.014）。几乎未发现标记的afMSCs，提示存在旁分泌效应。
羊膜间充质干细胞在羊膜内浓缩注射后可减轻实验性腹裂中的肠损伤。经羊膜干细胞治疗（TRASCET）可能成为腹裂治疗的一个实用组成部分。
