Dionigi Beatrice, Brazzo Joseph A, Ahmed Azra, Feng Christina, Wu Yaotang, Zurakowski David, Fauza Dario O
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA; Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, MA.
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA; Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, MA.
J Pediatr Surg. 2015 Jun;50(6):1037-41. doi: 10.1016/j.jpedsurg.2015.03.034. Epub 2015 Mar 14.
We sought to study the impact of trans-amniotic stem cell therapy (TRASCET) in the Chiari-II malformation in experimental spina bifida.
Sprague-Dawley fetuses (n=62) exposed to retinoic acid were divided into three groups at term (21-22 days gestation): untreated isolated spina bifida (n=21), isolated spina bifida treated with intra-amniotic injection of concentrated, syngeneic, labeled amniotic fluid mesenchymal stem cells (afMSCs) on gestational day 17 (n=28), and normal controls (n=13). Analyses included measurements of brainstem and cerebellar placement on high resolution MRI and histology. Statistical comparisons included ANOVA.
In parallel to the expected induced coverage of the spina bifida in the afMSC-treated group (P<0.001), there were statistically significant differences in brainstem displacement across the groups (P<0.001), with the highest caudal displacement in the untreated group. Significant differences in cerebellar displacement were also noted, albeit less pronounced. Pairwise comparisons were statistically significant, with P=0.014 between treated and normal controls in caudal brainstem displacement and P<0.001 for all other comparisons. Labeled afMSCs were identified in 71% of treated fetuses.
Induced coverage of spina bifida by TRASCET minimizes the Chiari-II malformation in the retinoic acid rodent model, further suggesting it as a practical alternative for the prenatal management of spina bifida.
我们试图研究经羊膜干细胞疗法（TRASCET）对实验性脊柱裂中Chiari-II畸形的影响。
将暴露于视黄酸的Sprague-Dawley胎儿（n = 62）在足月时（妊娠21 - 22天）分为三组：未经治疗的孤立性脊柱裂组（n = 21）、在妊娠第17天经羊膜腔内注射浓缩的、同基因的、标记的羊水间充质干细胞（afMSCs）治疗的孤立性脊柱裂组（n = 28）和正常对照组（n = 13）。分析包括在高分辨率MRI上测量脑干和小脑的位置以及组织学检查。统计比较采用方差分析。
与afMSC治疗组中预期的脊柱裂诱导覆盖情况一致（P < 0.001），各组间脑干移位存在统计学显著差异（P < 0.001），未治疗组的尾侧移位最大。小脑移位也存在显著差异，尽管不太明显。两两比较具有统计学意义，治疗组与正常对照组在脑干尾侧移位方面P = 0.014，其他所有比较P < 0.001。在71%的治疗胎儿中发现了标记的afMSCs。
TRASCET诱导的脊柱裂覆盖可使视黄酸啮齿动物模型中的Chiari-II畸形最小化，进一步表明它是脊柱裂产前管理的一种实用替代方法。
