Enhancement of Transamniotic Stem Cell Therapy for Spina Bifida by Genetic Engineering of Donor Mesenchymal Stem Cells with an Fgf2 Transgene
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In brief
In brief
Genetic engineering of donor mesenchymal stem cells with Fgf2 transgene significantly improves spina bifida defect coverage in transamniotic stem cell therapy, increasing coverage rates from 38.5% to 73.3% in a rodent model. This approach represents a promising enhancement strategy for prenatal treatment of neural tube defects.
Written by the GCMD Library team from the article.
Abstract
Background/Purpose
We examined whether engineered overexpression of fibroblast growth factor-2 (Fgf2) in donor mesenchymal stem cells (MSCs) could enhance spina bifida coverage induced by transamniotic stem cell therapy (TRASCET).
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 into all fetuses (n = 157) of either amniotic fluid-derived MSCs (afMSC; n = 85) or afMSCs transduced with an Fgf2 transgene (Fgf2-afMSC; n = 72) on gestational day 17 (term=21–22 days). Defect coverage was categorized at term by histology and pan-cytokeratin immunohistochemistry. Statistical coverage comparisons were by logistic regression.
Results
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 statistically significantly higher than in the untreated group (10%; p<0.001 for both). There was a significantly higher coverage rate 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. Genetic engineering of donor cells is a promising strategy for the enhancement of this emerging therapy.