Original Article
Donor mesenchymal stem cell linetics after transamniotic stem cell therapy (TRASCET) for experimental spina bifida

https://doi.org/10.1016/j.jpedsurg.2018.02.067Get rights and content

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.

Section snippets

Methods

This study was approved by the Boston Children's Hospital Institutional Animal Care and Use Committee under protocol #15–07-2951R.

Results

Overall fetal survival was 92% (132/144) and comparable between the groups that received cells (90%; 70/78), or luciferase alone (94%; 62/66). Among surviving fetuses, 60 (45%) had a neural tube defect, consisting of either an isolated spina bifida (54; 90%), or spina bifida associated with exencephaly (6; 10%).

Among survivors receiving intra-amniotic injections of labeled afMSCs (n = 31), donor afMSCs were identified solely in the placenta, umbilical cord, spleen, bone marrow, hip bones, defect,

Discussion

Prenatal repair of spina bifida has long been validated clinically and is now standard of care [10]. At the same time, it is not a cure and is justifiable only in a relatively limited patient cohort, as per rather stringent stratification criteria of candidate maternal-fetal units. Furthermore, in addition to its inherent risks to the mother and fetus, fetal surgery is feasible only relatively late into the pathophysiological process of this disease. Should it eventually prove clinically

Acknowledgement

This work was supported by the Kevin and Kate McCarey Fund for Surgical Research at Boston Children's Hospital. H.F.S. was supported by a Joshua Ryan Rappaport Fellowship from the Department of Surgery at Boston Children's Hospital.

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