Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA,
Fetal Diagn Ther. 2020;47(12):902-911. doi: 10.1159/000509244. Epub 2020 Sep 2.
Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can induce spina bifida coverage with neoskin. We initiated a mechanistic analysis of this host response.
Pregnant dams (n = 28) exposed to retinoic acid to induce fetal spina bifida were divided into an untreated group and 2 groups receiving intra-amniotic injections on gestational day 17 (E17; term = E21-22) of either amniotic fluid-derived MSCs (afMSCs; n = 105) or saline (n = 107). Gene expressions of multiple paracrine and cell clonality markers were quantified at term by RT-qPCR at the defect and fetal bone marrow. Defects were examined histologically for neoskin coverage. Comparisons were by Mann-Whitney U tests and logistic regression.
Defect coverage was associated with significant downregulation of both epidermal growth factor (Egf; p = 0.031) and fibroblast growth factor-2 (Fgf-2; p = 0.042) expressions at the defect and with significant downregulation of transforming growth factor-beta-1 (Tgfb-1; p = 0.021) and CD45 (p = 0.028) expressions at the fetal bone marrow.
Coverage of experimental spina bifida is associated with local and bone marrow negative feedback of select paracrine factors, as well as increased relative mesenchymal stem cell activity in the bone marrow. Further analyses informed by these findings may lead to strategies of nonsurgical induction of prenatal coverage of spina bifida.
经羊膜腔内注射间充质干细胞（MSCs）的透膜干细胞治疗（TRASCET）可以诱导脊柱裂缺损覆盖新生皮肤。我们对此种宿主反应的机制进行了分析。
将接受维甲酸暴露以诱导胎儿脊柱裂的妊娠母鼠（n = 28）分为未治疗组和 2 个治疗组，在妊娠第 17 天（E17；足月 = E21-22）经羊膜腔内分别注射羊水来源的 MSCs（afMSCs；n = 105）或生理盐水（n = 107）。通过 RT-qPCR 在 E17 时于缺陷处和胎儿骨髓中检测多种旁分泌和细胞克隆性标志物的基因表达。通过组织学检查缺陷处的新生皮肤覆盖情况。通过 Mann-Whitney U 检验和逻辑回归进行比较。
缺陷处的覆盖与缺陷处表皮生长因子（Egf；p = 0.031）和碱性成纤维细胞生长因子-2（Fgf-2；p = 0.042）表达的显著下调以及胎儿骨髓中转化生长因子-β-1（Tgfb-1；p = 0.021）和 CD45（p = 0.028）表达的显著下调相关。
实验性脊柱裂的覆盖与选择旁分泌因子的局部和骨髓负反馈以及骨髓中间充质干细胞活性的相对增加有关。进一步的分析可能会为非手术诱导胎儿脊柱裂的产前覆盖提供策略。
