Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, MA 02115, USA.
Department of Surgery, Boston Children's Hospital/Harvard Medical School, Boston, MA 02115, USA.
J Pediatr Surg. 2021 Jun;56(6):1226-1232. doi: 10.1016/j.jpedsurg.2021.02.036. Epub 2021 Feb 24.
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).
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.
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).
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.
背景/目的：我们研究了在供体细胞间充质干细胞（MSCs）中过表达成纤维细胞生长因子-2（Fgf2）是否能增强经羊膜腔干细胞治疗（TRASCET）诱导的脊柱裂覆盖。
将暴露于维甲酸以诱导胎儿脊柱裂的妊娠 Sprague-Dawley 孕鼠（n=24）分为三组。未处理组不进行进一步操作。两组均在妊娠第 17 天（足月= 21-22 天）向所有胎儿（n=157）的羊膜腔内注射体积匹配的羊水来源的 MSCs（afMSC；n=85）或转染 Fgf2 转基因的 afMSCs（Fgf2-afMSC；n=72）。通过组织学和全细胞角蛋白免疫组织化学在足月时对缺陷覆盖进行分类。通过逻辑回归进行统计覆盖比较。
在 84 例孤立性脊柱裂幸存者中，71 例有明确的组织学结果。afMSC 组（38.5%）和 Fgf2-afMSC 组（73.3%）的缺陷覆盖率均明显高于未处理组（均为 p<0.001）。Fgf2-afMSC 组的覆盖率明显高于 afMSC 组（p=0.025）。
在供体细胞间充质干细胞中过表达 Fgf2 可提高经羊膜腔干细胞治疗脊柱裂的啮齿动物模型中的缺陷覆盖率。对供体细胞进行基因工程是增强这种新兴治疗方法的有前途的策略。
