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Purpose: We sought to study the impact of trans-amniotic stem cell therapy (TRASCET) in the Chiari-II malformation in experimental spina bifida., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The proportions of select stem cells in term amniotic fluid have been shown to correlate with the type and size of experimental neural tube defects (NTDs). We sought to determine the impact of gestational age upon this form of targeted amniotic cell profiling., Methods: Sprague-Dawley fetuses with retinoic acid-induced NTDs (n = 110) underwent amniotic fluid procurement at four time points in gestation. Samples were analyzed by flow cytometry for the presence of cells concomitantly expressing Nestin and Sox-2 (neural stem cells, aNSCs) and cells concomitantly expressing CD29 and CD44 (mesenchymal stem cells, aMSCs). Statistical analysis was by nonparametric Kruskal-Wallis ANOVA (p < 0.05)., Results: There was a statistically significant impact of gestational age on the proportions of both aMSCs (p = 0.01) and aNSCs (p < 0.01) in fetuses with isolated spina bifida. No such impact was noted in normal fetuses (p > 0.10 for both cells), in isolated exencephaly (p > 0.10 for both cells), or in combination defects (p > 0.10 for both cells). Gestational age had no effect on aNSC/aMSC ratios., Conclusions: Targeted quantitative amniotic cell profiling varies with gestational age in experimental isolated spina bifida. This finding should be considered prior to the eventual translation of this diagnostic adjunct into the prenatal evaluation of these anomalies. © 2014 S. Karger AG, Basel.

Purpose: We sought to determine whether simple intra-amniotic delivery of concentrated amniotic mesenchymal stem cells (afMSCs) may elicit prenatal coverage of experimental spina bifida., Methods: Time-dated pregnant Sprague-Dawley dams (n=24) exposed to retinoic acid for the induction of fetal neural tube defects were divided in three groups. Group I had no further manipulations. Groups II and III received volume-matched intra-amniotic injections of either saline (Group II) or a suspension of syngeneic afMSCs labeled with green fluorescent protein (Group III) in all fetuses (n=202) on gestational day 17 (term=21-22 days). Animals were killed before term. Statistical comparisons were by ANOVA (P<0.05)., Results: Of 165 fetuses viable at euthanasia, a spina bifida was present in 58% (96/165), with no significant differences in defect dimension across the groups (P=0.19). However, variable degrees of coverage of the defect by a rudimentary skin confirmed histologically were only present in Group III (P<0.001), in which donor afMSCs were documented, with no differences between Groups I and II (P=0.98)., Conclusions: Amniotic mesenchymal stem cells can induce partial or complete coverage of experimental spina bifida after concentrated intra-amniotic injection. Trans-amniotic stem cell therapy (TRASCET) may become a practical option in the prenatal management of spina bifida., (Copyright © 2015 Elsevier Inc. All rights reserved.)