Transamniotic stem cell therapy (TRASCET) in a leporine model of gastroschisis.
OBJECTIVE
Transamniotic stem cell therapy (TRASCET) with amniotic fluid mesenchymal stem cells (afMSCs) has been shown to mitigate bowel damage in a rodent model of gastroschisis. As a prerequisite to clinical translation, we sought to study TRASCET in a larger animal model.


METHODS
New Zealand rabbit fetuses (n=64) with surgically created gastroschisis were divided into three groups. One group (untreated) had no further manipulations. Two groups received volume-matched intraamniotic injections of either saline or a suspension of afMSCs. Nonmanipulated fetuses served as controls. Histomorphologic measurements of intestinal damage, along with biochemical profiling of inflammation markers, were performed at term. Statistical comparisons were by Fisher's exact test, ANOVA and the Wald test (P<0.05).


RESULTS
Overall survival was 62.5%. Segmental and total intestinal wall thicknesses were significantly decreased in the afMSC group compared with the untreated and saline groups (all P<0.001), with no significant differences between untreated and saline groups (P=0.24 to 1.00, depending on layer). Muscularis and serosal layers were significantly thicker in the afMSC group than in normal controls (P=0.045 and P<0.001, respectively).


CONCLUSIONS
Concentrated intraamniotic injection of afMSC lessens, yet does not prevent, intestinal damage in a leporine model of gastroschisis. TRASCET may become a valuable strategy in the management of gastroschisis.


METHODS
N/A - animal/experimental studies.
Department of Surgery, 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.
Christopher D
CD
Graham
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA.
Hester F
HF
Shieh
Department of Surgery, 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.
John Patrick
JP
Connors
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA.
Lucas
L
Rohrer
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA.
Alexander
A
Papadakis
Department of Surgery, 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. Electronic address: dario.fauza@childrens.harvard.edu.
Dario O
DO
Fauza
D000653:Amniotic Fluid; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020139:Gastroschisis / Q000150:complications / Q000473:pathology / Q000628:therapy*; D007249:Inflammation / Q000209:etiology; D007267:Injections; D007422:Intestines / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D011817:Rabbits
Amniotic mesenchymal stem cells; Fetal stem cells; Gastroschisis; Transamniotic stem cell therapy