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经皮移植人脐带血源多能干细胞治疗犬脊髓损伤模型。

Percutaneous transplantation of human umbilical cord blood-derived multipotent stem cells in a canine model of spinal cord injury.

机构信息

Department of Veterinary Surgery, Konkuk University, Seoul, Republic of Korea.

出版信息

J Neurosurg Spine. 2009 Dec;11(6):749-57. doi: 10.3171/2009.6.SPINE08710.

Abstract

OBJECT

The authors describe a method for percutaneous transplantation of human umbilical cord blood (hUCB)-derived multipotent stem cells (MSCs) under fluoroscopic guidance. The investigators then tested whether percutaneous transplantation of hUCB-derived MSCs improved neurological functional recovery after acute spinal cord injury (SCI).

METHODS

The authors induced SCI in 10 dogs by percutaneous balloon compression. The 10 injured dogs were assigned randomly to the following groups (2 dogs each): Group 1, evaluated 2 weeks after sham transplantation; Group 2, evaluated 2 weeks after transplantation; Group 3, evaluated 4 weeks after sham transplantation; Group 4, evaluated 4 weeks after transplantation; and Group 5, evaluated 4 weeks after multispot transplantations. The dogs with sham transplantation (Groups 1 and 3) received the same volume of saline, as a control. A spinal needle was advanced into the spinal canal, and the investigators confirmed that the end of the spinal needle was located in the ventral part of spinal cord parenchyma by using contrast medium under fluoroscopic guidance. The hUCB-derived MSCs were transplanted into the cranial end of the injured segment in 6 injured dogs at 7 days after SCI.

RESULTS

Two dogs in Group 2 showed no improvement until 2 weeks after transplantation. Three of 4 dogs (Groups 4 and 5) that received cellular transplants exhibited gradual improvement in hindlimb locomotion from 3 weeks after cell transplantation. The CM-DiI-labeled hUCB-derived MSCs were observed in the spinal cord lesions at 4 weeks posttransplantation and exerted a significant beneficial effect by reducing cyst and injury size. The transplanted cells were positive for NeuN, glial fibrillary acidic protein, and von Willebrand factor.

CONCLUSIONS

The percutaneous transplantation technique described here can be easily performed, and it differs from previous techniques by avoiding surgical exposure and allowing cells to be more precisely transplanted into the spinal cord. This technique has many potential applications in the treatment of human SCI by cell transplantation. The results also suggest that transplantation of hUCB-derived MSCs may have therapeutic effects that decrease cavitation for acute SCI.

摘要

目的

作者描述了一种在透视引导下经皮移植人脐血(hUCB)衍生多能干细胞(MSCs)的方法。然后,研究者测试了经皮移植 hUCB 衍生 MSCs 是否能改善急性脊髓损伤(SCI)后的神经功能恢复。

方法

作者通过经皮球囊压迫诱导 10 只狗的 SCI。将这 10 只受伤的狗随机分为以下几组(每组 2 只):假移植组 1,在假移植后 2 周评估;移植组 2,在移植后 2 周评估;假移植组 3,在假移植后 4 周评估;移植组 4,在移植后 4 周评估;多部位移植组 5,在移植后 4 周评估。假移植组(1 组和 3 组)接受相同体积的生理盐水,作为对照。通过透视引导下的造影剂,将一根脊柱针推进椎管,研究人员确认脊柱针的末端位于脊髓实质的腹侧。在 SCI 后 7 天,将 hUCB 衍生的 MSCs 移植到 6 只受伤狗的损伤段颅端。

结果

2 只移植组 2 的狗在移植后 2 周内没有改善。4 只接受细胞移植的狗中的 3 只(4 组和 5 组)从细胞移植后 3 周开始后肢运动逐渐改善。移植后 4 周,可在脊髓损伤处观察到 CM-DiI 标记的 hUCB 衍生 MSCs,并通过减少囊肿和损伤体积产生显著的有益效果。移植细胞对 NeuN、胶质纤维酸性蛋白和血管性血友病因子呈阳性。

结论

这里描述的经皮移植技术操作简单,与以前的技术不同之处在于避免了手术暴露,并允许更精确地将细胞移植到脊髓中。该技术在通过细胞移植治疗人类 SCI 方面具有许多潜在的应用。结果还表明,移植 hUCB 衍生 MSCs 可能具有治疗作用,可减少急性 SCI 的空洞化。

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