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Trans-Amniotic Stem Cell Therapy (TRASCET) for Experimental Spina Bifida
Beatrice Dionigi, Azra Ahmed, Joseph Brazzo III, John Patrick Connors, David Zurakowski, *Dario O. Fauza
Boston Children’s Hospital, Boston, MA

Purpose: Surgical prenatal coverage of spina bifida is associated with significant complications, most notably preterm labor. Amniotic mesenchymal stem cells (aMSCs) have been shown to enhance normal fetal wound healing. We hypothesized that simple intra-amniotic delivery of large amounts of aMSCs may elicit some degree of repair of the spina bifida defect.

Methods: Pregnant Sprague-Dawley dams (n=24) exposed to retinoic acid for the induction of fetal neural tube defects were divided into three groups. Group I had no manipulations. Groups II and III received volume-matched intra-amniotic injections of either saline (group II) or a suspension of 2x106 cells/mL of aMSCs (group III) blindly in all fetuses (n=202) on gestational day 17 (term=21-22 days). Infused aMSCs consisted of syngeneic Lewis rat cells with identity confirmed by flow cytometry Animals were killed before term. Statistical comparisons were by ANOVA (P<0.05).

Results: A total of 165 fetuses were viable at euthanasia. Among fetuses with spina bifida (96/165; 58%), there were no significant differences in the overall dimensions of the discernible defect across the groups (P=0.19). However, there was a statistically significant increase in the proportion of fetuses with variable degrees of coverage (some complete) of the defect by a thin, rudimentary skin, confirmed histologically, in group III (P<0.001), with no differences between groups I and II (P=0.98). Donor aMSCs were identified in 83% (33/40) of the fetuses in that group via immunohistochemistry for GFP.

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, easily accessible, minimally invasive option in the prenatal management of spina bifida.

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