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Trans-Amniotic Stem Cell Therapy Minimizes Chiari-II Malformation in Experimental Spina Bifida
Beatrice Dionigi, MD; Joseph Brazzo III, BS; Azra Ahmed, BS; Christina Feng, MD; Yaotang Wu, PhD; David Zurakowski, PhD; Dario O Fauza, MD, PhD
Boston Children’s Hospital, Boston MA

Background:
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:
As expected, there was a statistically significant increase in the proportion of fetuses with variable degrees of coverage of the spina bifida by a rudimentary skin confirmed histologically in the afMSC-treated group (P<0.001). Overall, there were statistically significant differences across the groups in linear and angular measurements of brainstem placement (P<0.001), with the untreated group displaying the highest caudal displacement. All pairwise comparisons were statistically significant, with P=0.014 between treated and normal controls in angular brainstem (caudal) displacement and P<0.001 for all other angular and linear pairwise comparisons. Differences in cerebellar placement were also noted with P<0.001 overall and significance in most pairwise comparisons, except between treated and untreated groups (P=0.10). Donor afMSCs were identified in 71% (20/28) of fetuses in the treated group via immunohistochemistry for GFP.

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.



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