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成年大鼠海马祖细胞种植在胶原支架上,植入穿透性脑损伤大鼠模型中。

Implantation of a collagen scaffold seeded with adult rat hippocampal progenitors in a rat model of penetrating brain injury.

机构信息

Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

出版信息

J Neurosci Methods. 2012 Jul 30;209(1):199-211. doi: 10.1016/j.jneumeth.2012.06.003. Epub 2012 Jun 12.

Abstract

Penetrating brain injury (PBI) is a complex central nervous system injury in which mechanical damage to brain parenchyma results in hemorrhage, ischemia, broad areas of necrosis, and eventually cavitation. The permanent loss of brain tissue affords the possibility of treatment using a biomaterial scaffold to fill the lesion site and potentially deliver pharmacological or cellular therapeutic agents. The administration of cellular therapy may be of benefit in both mitigating the secondary injury process and promoting regeneration through replacement of certain cell populations. This study investigated the survival and differentiation of adult rat hippocampal neural progenitor cells delivered by a collagen scaffold in a rat model of PBI. The cell-scaffold construct was implanted 1 week after injury and was observed to remain intact with open pores upon analysis 4 weeks later. Implanted neural progenitors were found to have survived within the scaffold, and also to have migrated into the surrounding brain. Differentiated phenotypes included astrocytes, oligodendrocytes, vascular endothelial cells, and possibly macrophages. The demonstrated multipotency of this cell population in vivo in the context of traumatic brain injury has implications for regenerative therapies, but additional stimulation appears necessary to promote neuronal differentiation outside normally neurogenic regions.

摘要

穿透性脑损伤(PBI)是一种复杂的中枢神经系统损伤,其中脑实质的机械损伤导致出血、缺血、广泛的坏死,最终导致空洞形成。脑组织的永久性丧失为使用生物材料支架治疗提供了可能性,以填充病变部位,并有可能输送药物或细胞治疗剂。细胞治疗的给药可能有助于减轻继发性损伤过程,并通过替代某些细胞群来促进再生。本研究在 PBI 大鼠模型中,通过胶原支架研究了成年大鼠海马神经祖细胞的存活和分化。细胞-支架构建体在损伤后 1 周植入,4 周后分析时发现仍保持完整,具有开放的孔。植入的神经祖细胞被发现存在于支架内,并且已经迁移到周围的大脑中。分化的表型包括星形胶质细胞、少突胶质细胞、血管内皮细胞,可能还有巨噬细胞。在创伤性脑损伤的背景下,这种细胞群体在体内的多能性表明它对再生治疗具有重要意义,但需要额外的刺激来促进正常神经发生区域以外的神经元分化。

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