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人类神经干细胞移植用于灵长类动物脊髓损伤的研究

Transplantation of human neural stem cells for spinal cord injury in primates.

作者信息

Iwanami A, Kaneko S, Nakamura M, Kanemura Y, Mori H, Kobayashi S, Yamasaki M, Momoshima S, Ishii H, Ando K, Tanioka Y, Tamaoki N, Nomura T, Toyama Y, Okano H

机构信息

Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.

出版信息

J Neurosci Res. 2005 Apr 15;80(2):182-90. doi: 10.1002/jnr.20436.

Abstract

Recent studies have shown that delayed transplantation of neural stem/progenitor cells (NSPCs) into the injured spinal cord can promote functional recovery in adult rats. Preclinical studies using nonhuman primates, however, are necessary before NSPCs can be used in clinical trials to treat human patients with spinal cord injury (SCI). Cervical contusion SCIs were induced in 10 adult common marmosets using a stereotaxic device. Nine days after injury, in vitro-expanded human NSPCs were transplanted into the spinal cord of five randomly selected animals, and the other sham-operated control animals received culture medium alone. Motor functions were evaluated through measurements of bar grip power and spontaneous motor activity, and temporal changes in the intramedullary signals were monitored by magnetic resonance imaging. Eight weeks after transplantation, all animals were sacrificed. Histologic analysis revealed that the grafted human NSPCs survived and differentiated into neurons, astrocytes, and oligodendrocytes, and that the cavities were smaller than those in sham-operated control animals. The bar grip power and the spontaneous motor activity of the transplanted animals were significantly higher than those of sham-operated control animals. These findings show that NSPC transplantation was effective for SCI in primates and suggest that human NSPC transplantation could be a feasible treatment for human SCI.

摘要

最近的研究表明,将神经干细胞/祖细胞(NSPCs)延迟移植到受损脊髓中可促进成年大鼠的功能恢复。然而,在将NSPCs用于治疗脊髓损伤(SCI)人类患者的临床试验之前,有必要进行使用非人类灵长类动物的临床前研究。使用立体定向装置在10只成年普通狨猴中诱导颈椎挫伤性SCI。损伤9天后,将体外扩增的人NSPCs移植到5只随机选择的动物的脊髓中,其他假手术对照动物仅接受培养基。通过测量握力和自发运动活动来评估运动功能,并通过磁共振成像监测髓内信号的时间变化。移植8周后,处死所有动物。组织学分析显示,移植的人NSPCs存活并分化为神经元、星形胶质细胞和少突胶质细胞,并且空洞比假手术对照动物中的小。移植动物的握力和自发运动活动明显高于假手术对照动物。这些发现表明,NSPC移植对灵长类动物的SCI有效,并表明人NSPC移植可能是治疗人类SCI的可行方法。

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