Beatrice Dionigi1, Joseph A Brazzo1, Azra Ahmed1, Christina Feng1, Yaotang Wu1, David Zurakowski1, Dario O Fauza2. 1. 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. 2. 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. Electronic address: dario.fauza@childrens.harvard.edu.
Abstract
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.
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.
Authors: Sandra K Kabagambe; Y Julia Chen; Melissa A Vanover; Payam Saadai; Diana L Farmer Journal: Childs Nerv Syst Date: 2017-05-11 Impact factor: 1.475
Authors: Nathan Maassel; James Farrelly; Daniel Coman; Mollie Freedman-Weiss; Samantha Ahle; Sarah Ullrich; Nicholas Yung; Fahmeed Hyder; David Stitelman Journal: PLoS One Date: 2021-06-30 Impact factor: 3.240