Neural stem cell delivery to the spinal cord in an ovine model of fetal surgery for spina bifida
Neural stem cell delivery to the spinal cord in an ovine model of fetal surgery for spina bifida
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DOI：
10.1016/j.surg.2008.05.009
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发表时间：
2008-09-01
期刊：
影响因子：
3.8
通讯作者：
Snyder, Evan Y.
中科院分区：
文献类型：
--
作者：
Fauza, Dario O.;Jennings, Russell W.;Snyder, Evan Y.
背景我们介绍了产前神经干细胞（NSC）交付的概念，脊髓作为一种辅助胎儿脊柱裂的修复。将患有实验性脊髓脊膜膨出（MMC; n = 25）的胎羊分为3组：组I，无修复;组II，标准手术MMC覆盖;和组III，MMC覆盖加小鼠NSC克隆到脊髓缺损中的递送。供体细胞组成型表达编码大肠杆菌β-半乳糖苷酶的lacZ，但它们通过暴露BrdU和/或荧光膜染料PKH-26进一步标记。出生后不久进行盲法初始临床评估和多脊髓分析。与II组和III组相比，I组的生存率和严重下肢轻瘫的发生率均显著更差。在第三组中，神经干细胞密度最高的信号索的最受损的地区，在这些地区的选择性植入。供体神经干细胞在体内保持未分化状态，在缺陷内产生神经营养因子。第III组中没有动物在这种干预后病情恶化。神经干细胞保持未分化状态，并在短期内产生神经营养因子后交付到胎儿脊髓，在实验MMC的设置。将NSC递送至脊髓作为针对脊柱裂的治疗策略是有必要的。
Background. We introduce the notion of prenatal neural stein cell (NSC) delivery, to the spinal cord as an adjuvant to fetal repair of spina bifida.Methods. Fetal lambs with experimental myelomeningocele (MMC; n = 25) were divided in 3 groups: group I, no repair; group II, standard surgical MMC coverage; and group III, MMC coverage plus delivery, of a murine NSCs clone into the spinal cord defect. Donor cells constitutively expressed lacZ encoding for Escherichia coli beta-galactosidase, yet they were further labeled by exposure either BrdU and/or to the fluorescent membrane dye PKH-26. Blinded initial clinical evaluations and multiple spinal cord analyses were undertaken soon after birth.Results. Both survival and the incidence of major paraparesis were significantly worse in group I compared with groups II and III. In group III, NSC density was highest within the most damaged areas of the signal cord, with selective engraftment within those regions. Donor NSCs retained an undifferentiated state in vivo, producing neurotrophic factors within the defect. No animals in group III had a worsened condition following this intervention.Conclusions. Neural stem cells retain an undifferentiated state and produce neurotrophic factors in the short term after delivery to the fetal spinal cord, in the setting of experimental MMC. Further scrutiny of NSC delivery to the spinal cord as a therapeutic strategy against spina bifida is warranted.