Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Fetal Diagn Ther. 2013;34(1):38-43. doi: 10.1159/000350267. Epub 2013 Apr 26.
Neural stem cells (NSCs) may promote spinal cord repair in fetuses with experimental spina bifida. We sought to determine the fate of amniotic-derived NSCs (aNSCs) after simple intra-amniotic injection in a syngeneic model of spina bifida.
Fetal neural tube defects were induced on 20 pregnant Lewis dams by prenatal administration of retinoic acid. Ten dams served as amniotic fluid donors for epigenetic isolation of aNSCs, which were expanded and labeled with 5-bromo-2'-deoxyuridine. The remaining 10 dams received intra-amniotic injections of the processed aNSCs, blindly in all their fetuses (n = 37) on gestational day 17 (term = E21-22). Fetuses with spina bifida underwent screening for the presence of donor aNSCs in the spinal cord at term.
Donor cells were identified in 93.3% of the animals with spina bifida, selectively populating the neural placode, typically in clusters, retaining an undifferentiated morphology, and predominantly on exposed neural surfaces, though some were detected deeper in neighboring neural tissue.
The amniotic cavity can serve as a route of administration of NSCs in experimental spina bifida. Simple intra-amniotic delivery of NSCs may be a practical adjuvant to regenerative strategies for the treatment of spina bifida.
神经干细胞(NSCs)可能促进实验性脊柱裂胎儿的脊髓修复。我们试图确定在脊柱裂的同基因模型中,单纯羊膜内注射后,羊膜源性神经干细胞(aNSCs)的命运。
通过产前给予维甲酸诱导 20 只妊娠 Lewis 母鼠胎儿神经管缺陷。10 只母鼠作为胚胎神经干细胞的表观遗传学分离的羊水供体,将其扩增并标记为 5-溴-2'-脱氧尿苷。其余 10 只母鼠在妊娠第 17 天(足月为 E21-22)对所有胎儿(n = 37)进行处理后的 aNSCs 羊膜内注射。在足月时对脊柱裂胎儿进行筛查,以确定脊髓中是否存在供体 aNSCs。
在 93.3%的脊柱裂动物中鉴定出供体细胞,选择性地定位于神经嵴,通常呈簇状,保持未分化的形态,主要位于暴露的神经表面,但也有一些位于邻近神经组织的深部。
羊膜腔可以作为实验性脊柱裂中 NSCs 给药的途径。简单的羊膜内 NSCs 递送可能是治疗脊柱裂的再生策略的一种实用辅助方法。