Hester F Shieh1, Azra Ahmed1, Lucas Rohrer1, David Zurakowski1, Dario O Fauza2. 1. Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA. 2. Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA. Electronic address: dario.fauza@childrens.harvard.edu.
Abstract
PURPOSE: We sought to examine donor mesenchymal stem cell (MSC) kinetics after transamniotic stem cell therapy (TRASCET) in experimental spina bifida. METHODS: Pregnant Sprague-Dawley dams exposed to retinoic acid for the induction of fetal neural tube defects received volume-matched intra-amniotic injections on gestational day 17 (E17; term=E22): either amniotic fluid MSCs (afMSCs) labeled with a luciferase reporter gene (n=78), or luciferase protein alone (n=66). Samples from twelve organ systems from each surviving fetus with spina bifida (total n=60) were screened via microplate luminometry at term. RESULTS: Donor afMSCs were identified exclusively in the placenta, umbilical cord, spleen, bone marrow, hip bones, defect, and brain. Luminometry was negative in control fetuses receiving luciferase alone (p<0.001). Signal intensity in relative light units (RLUs) was moderately correlated between the defect and the hip bones (rho=0.38, p=0.048), and between the placenta and the brain (rho=0.40, p=0.038). CONCLUSIONS: Amniotic mesenchymal stem cells engraft to specific sites after concentrated intra-amniotic injection in the setting of spina bifida. A hematogenous route encompassing the bone marrow as well as distant central nervous system homing are fundamental constituents of cell trafficking. These findings must be considered during eventual patient selection for transamniotic stem cell therapy in the prenatal management of spina bifida.
PURPOSE: We sought to examine donor mesenchymal stem cell (MSC) kinetics after transamniotic stem cell therapy (TRASCET) in experimental spina bifida. METHODS: Pregnant Sprague-Dawley dams exposed to retinoic acid for the induction of fetal neural tube defects received volume-matched intra-amniotic injections on gestational day 17 (E17; term=E22): either amniotic fluid MSCs (afMSCs) labeled with a luciferase reporter gene (n=78), or luciferase protein alone (n=66). Samples from twelve organ systems from each surviving fetus with spina bifida (total n=60) were screened via microplate luminometry at term. RESULTS:Donor afMSCs were identified exclusively in the placenta, umbilical cord, spleen, bone marrow, hip bones, defect, and brain. Luminometry was negative in control fetuses receiving luciferase alone (p<0.001). Signal intensity in relative light units (RLUs) was moderately correlated between the defect and the hip bones (rho=0.38, p=0.048), and between the placenta and the brain (rho=0.40, p=0.038). CONCLUSIONS: Amniotic mesenchymal stem cells engraft to specific sites after concentrated intra-amniotic injection in the setting of spina bifida. A hematogenous route encompassing the bone marrow as well as distant central nervous system homing are fundamental constituents of cell trafficking. These findings must be considered during eventual patient selection for transamniotic stem cell therapy in the prenatal management of spina bifida.
Authors: John W Steele; Sharon Bayliss; John Bayliss; Ying Linda Lin; Bogdan J Wlodarczyk; Robert M Cabrera; Yohannes G Asfaw; Thomas J Cummings; Richard H Finnell; Timothy M George Journal: J Pediatr Surg Date: 2019-06-29 Impact factor: 2.545
Authors: Yada Kunpalin; Sindhu Subramaniam; Silvia Perin; Mattia F M Gerli; Jan Bosteels; Sebastien Ourselin; Jan Deprest; Paolo De Coppi; Anna L David Journal: Prenat Diagn Date: 2021-01-11 Impact factor: 3.242