Trans-amniotic stem cell therapy (TRASCET) minimizes Chiari-II malformation in experimental spina bifida.
OBJECTIVE
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.
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.
Beatrice
B
Dionigi
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.
Joseph A
JA
Brazzo
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.
Azra
A
Ahmed
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.
Christina
C
Feng
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.
Yaotang
Y
Wu
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.
David
D
Zurakowski
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.
Dario O
DO
Fauza
D000650:Amnion; D000818:Animals; D001139:Arnold-Chiari Malformation / Q000196:embryology / Q000209:etiology / Q000517:prevention & control*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D046128:Fetal Therapies / Q000379:methods*; D015316:Genetic Therapy; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D016135:Spinal Dysraphism / Q000150:complications / Q000196:embryology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*
Amniotic mesenchymal stem cells; Chiari II malformation; Fetal therapy; Fetal wound healing; Myelomeningocele; Regenerative medicine; Spina bifida