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将神经胶质限制前体细胞急性移植到脊髓挫伤损伤中:存活、分化及其对损伤环境和轴突再生的影响。

Acute transplantation of glial-restricted precursor cells into spinal cord contusion injuries: survival, differentiation, and effects on lesion environment and axonal regeneration.

作者信息

Hill Caitlin E, Proschel Christoph, Noble Mark, Mayer-Proschel Margot, Gensel John C, Beattie Michael S, Bresnahan Jacqueline C

机构信息

STAR Laboratories, The Laboratory for Neural Repair, Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.

出版信息

Exp Neurol. 2004 Dec;190(2):289-310. doi: 10.1016/j.expneurol.2004.05.043.

Abstract

Transplantation of stem cells and immature cells has been reported to ameliorate tissue damage, induce axonal regeneration, and improve locomotion following spinal cord injury. However, unless these cells are pushed down a neuronal lineage, the majority of cells become glia, suggesting that the alterations observed may be potentially glially mediated. Transplantation of glial-restricted precursor (GRP) cells--a precursor cell population restricted to oligodendrocyte and astrocyte lineages--offers a novel way to examine the effects of glial cells on injury processes and repair. This study examines the survival and differentiation of GRP cells, and their ability to modulate the development of the lesion when transplanted immediately after a moderate contusion injury of the rat spinal cord. GRP cells isolated from a transgenic rat that ubiquitously expresses heat-stable human placental alkaline phosphatase (PLAP) were used to unambiguously detect transplanted GRP cells. Following transplantation, some GRP cells differentiated into oligodendrocytes and astrocytes, retaining their differentiation potential after injury. Transplanted GRP cells altered the lesion environment, reducing astrocytic scarring and the expression of inhibitory proteoglycans. Transplanted GRP cells did not induce long-distance regeneration from corticospinal tract (CST) and raphe-spinal axons when compared to control animals. However, GRP cell transplants did alter the morphology of CST axons toward that of growth cones, and CST fibers were found within GRP cell transplants, suggesting that GRP cells may be able to support axonal growth in vivo after injury.

摘要

据报道,干细胞和未成熟细胞移植可改善脊髓损伤后的组织损伤、诱导轴突再生并改善运动能力。然而,除非这些细胞被诱导分化为神经元谱系,否则大多数细胞会变成神经胶质细胞,这表明观察到的改变可能是由神经胶质细胞介导的。移植神经胶质限制前体细胞(GRP细胞)——一种仅限于少突胶质细胞和星形胶质细胞谱系的前体细胞群——为研究神经胶质细胞对损伤过程和修复的影响提供了一种新方法。本研究检测了GRP细胞在大鼠脊髓中度挫伤损伤后立即移植时的存活和分化情况,以及它们调节损伤发展的能力。从普遍表达热稳定人胎盘碱性磷酸酶(PLAP)的转基因大鼠中分离出的GRP细胞用于明确检测移植的GRP细胞。移植后,一些GRP细胞分化为少突胶质细胞和星形胶质细胞,在损伤后仍保留其分化潜能。移植的GRP细胞改变了损伤环境,减少了星形胶质瘢痕形成和抑制性蛋白聚糖的表达。与对照动物相比,移植的GRP细胞未诱导皮质脊髓束(CST)和中缝脊髓轴突的长距离再生。然而,GRP细胞移植确实使CST轴突的形态向生长锥方向改变,并且在GRP细胞移植区内发现了CST纤维,这表明GRP细胞可能能够在损伤后支持体内轴突生长。

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