Massachusetts Chapter of the American College of Surgeons

Back to 2020 Posters


Enhancement of Transamniotic Stem Cell Therapy for Spina Bifida by Genetic Engineering of Donor Mesenchymal Stem Cells with an Fgf2 Transgene
Stefanie P Lazow, MD; Daniel F Labuz, MD; Ina Kycia, PhD; David Zurakowski, PhD; Dario O Fauza, MD, PhD
Boston Children's Hospital, Boston, MA

Background: Transamniotic stem cell therapy (TRASCET) with amniotic fluid-derived mesenchymal stem cells (afMSCs) induces prenatal coverage of experimental spina bifida in some fetuses. Variation in defect fibroblast growth factor-2 (Fgf2) expression is associated with increased coverage. We examined whether overexpression of Fgf2 in donor afMSCs could enhance coverage rates.
Methods: Pregnant Sprague-Dawley dams (n=24) exposed to retinoic acid for induction of fetal spina bifida were divided in three groups. An untreated group had no further manipulations. Two groups received volume-matched intra-amniotic injections of labeled afMSCs, either without further manipulation (afMSC; n=85) or transduced to overexpress Fgf2 (Fgf2-afMSC; n=72) on gestational day 17 (term=21-22 days). afMSCs were syngeneic Lewis rat cells phenotyped by flow cytometry. Fgf2 mRNA expression and protein levels were measured by RT-qPCR and ELISA, respectively, in both cell populations. Defect coverage was histologically categorized at term and compared by logistic regression.
Results: Fgf2 mRNA expression and protein levels were 10.1-fold and 3.1-fold higher, respectively, in Fgf2-afMSCs than in afMSCs. Among 84 survivors with isolated spina bifida, 71 had definitive histology. Defect coverage rates in both the afMSC (38.5%) and Fgf2-afMSC (73.3%) groups were significantly higher than in the untreated group (10%; p<0.001 for both). There was a significantly higher rate of coverage in the Fgf2-afMSC group compared with the afMSC group (p=0.025). Conclusions: Fgf2 overexpression in donor mesenchymal stem cells increases defect coverage rates in a rodent model of transamniotic stem cell therapy for spina bifida and represents a promising strategy for the enhancement of this emerging therapy.


Back to 2020 Posters