title: Partial or complete coverage of experimental spina bifida by simple intra-amniotic injection of concentrated amniotic mesenchymal stem cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Dionigi
authors.affiliation: Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Azra
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Joseph
authors.initials: J
authors.lastname: Brazzo
authors.affiliation: Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: John Patrick
authors.initials: JP
authors.lastname: Connors
authors.affiliation: Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Zurakowski
authors.affiliation: Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: dario.fauza@childrens.harvard.edu.
authors.forename: Dario O
authors.initials: DO
authors.lastname: Fauza
mesh_terms: D000650:Amnion; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007267:Injections / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000473:pathology; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D016135:Spinal Dysraphism / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*
keywords: Amniotic mesenchymal stem cells; Fetal therapy; Fetal wound healing; Myelomeningocele; Regenerative medicine; Spina bifida; Tissue engineering