New England Surgical Society

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Repeat Dosing in the Retinoic Acid Model of Transamniotic Stem Cell Therapy for Spina Bifida
*Sarah Tracy1, *Alexander Chalphin1, *Stefanie Lazow1, *Ina Kycia2, *Christopher Chan3, *Adam Finkelstein4, *David Zurakowski2, Dario Fauza2
1Boston Children's Hospital and Beth Israel Deaconess Medical Center, Boston, MA;2Boston Children's Hospital, Boston, MA;3Boston University, Boston, MA;4Lafayette College, Easton, PA

Objective: We sought to examine the impact of repeat dosing in transamniotic stem cell therapy (TRASCET) for spina bifida in the rodent model. Design: Time-dated Sprague-Dawley fetuses with retinoic acid-induced neural tube defects were divided into three groups: one untreated (n=32) and two groups receiving volume-matched intra-amniotic injections of concentrated, labeled amniotic fluid mesenchymal stem cells (afMSCs) at either one (n=52), or two (n=99) time-points in gestation. Defect coverage was categorized histologically by the presence of an overlying neoskin at term. Statistical comparisons were by the Wald test (p<0.05).Results: Fetal survival to term was 85% (44/52) after a single injection and 38% (38/99) after two injections (p<0.001). Among those with isolated spina bifida (n=82), there was a statistically significant higher defect coverage rate (partial or complete) after a single injection vs. dual injection (p=0.019) and vs. no treatment (p<0.001), with no significant differences between the dual injection and untreated groups (p=0.357). Labeled cells were detected comparably in both treatment groups, homing to bone. Conclusions: Transamniotic stem cell therapy appears to lead to a lasting host response to the injected donor cells. Further mechanistic insight into this response could lead to additional non-surgical strategies for prenatal coverage of spina bifida.


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