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冷冻保存的人胚胎癌衍生神经元(NT2N细胞)移植可促进缺血大鼠的功能恢复。

Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats.

作者信息

Borlongan C V, Tajima Y, Trojanowski J Q, Lee V M, Sanberg P R

机构信息

Department of Surgery, University of South Florida College of Medicine, Tampa 33612, USA.

出版信息

Exp Neurol. 1998 Feb;149(2):310-21. doi: 10.1006/exnr.1997.6730.

Abstract

This study was designed to explore the efficacy of a human clone cell line as an alternative neural graft source and to validate the practice of cryopreservation and xenografting as logistical approaches toward conducting neural transplantation. We investigated the biological effects of transplanting cultured human neurons (NT2N cells) derived from a well-characterized embryonal carcinoma cell line into the brains of rats subjected to transient, focal cerebral ischemia induced by embolic occlusion of the middle cerebral artery. At 1 month and extending throughout the 6-month posttransplantation test period, ischemic animals that were transplanted with NT2N cells and treated with an immunosuppressive drug displayed a significant improvement in a passive avoidance task as well as a normalization of asymmetrical motor behavior compared to ischemic animals that received rat fetal cerebellar cell grafts or vehicle alone. Remarkably, cryopreserved NT2N cell grafts compared with fresh NT2N cell grafts, remained viable in the immunosuppressed rat brain and effective in producing behavioral recovery in immunosuppressed ischemic animals. The long-term viability of cryopreserved NT2N cell xenografts in vivo and their sustained effectiveness in promoting behavioral recovery suggest potential utilization of xenografting and cryopreservation as useful protocols for establishing clone cell lines as graft source in neural transplantation therapies for central nervous system disorders.

摘要

本研究旨在探索一种人类克隆细胞系作为替代神经移植源的功效,并验证冷冻保存和异种移植作为开展神经移植的后勤手段的可行性。我们研究了将源自特征明确的胚胎癌细胞系的培养人类神经元(NT2N细胞)移植到因大脑中动脉栓塞闭塞导致短暂性局灶性脑缺血的大鼠脑内的生物学效应。在移植后1个月及整个6个月的测试期内,与接受大鼠胎儿小脑细胞移植或仅接受赋形剂的缺血动物相比,接受NT2N细胞移植并接受免疫抑制药物治疗的缺血动物在被动回避任务中表现出显著改善,不对称运动行为也恢复正常。值得注意的是,与新鲜NT2N细胞移植相比,冷冻保存的NT2N细胞移植在免疫抑制的大鼠脑内仍保持存活,并能有效促进免疫抑制的缺血动物的行为恢复。冷冻保存的NT2N细胞异种移植在体内的长期存活及其在促进行为恢复方面的持续有效性表明,异种移植和冷冻保存有可能作为有用的方案,用于在中枢神经系统疾病的神经移植治疗中建立克隆细胞系作为移植源。

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