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将人骨髓源性基质细胞移植到受损脊髓后功能的恢复。

Recovery of function following grafting of human bone marrow-derived stromal cells into the injured spinal cord.

作者信息

Himes B Timothy, Neuhuber Birgit, Coleman Carl, Kushner Robert, Swanger Sharon A, Kopen Gene C, Wagner Joseph, Shumsky Jed S, Fischer Itzhak

机构信息

Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.

出版信息

Neurorehabil Neural Repair. 2006 Jun;20(2):278-96. doi: 10.1177/1545968306286976.

Abstract

This study evaluates functional recovery after transplanting human bone marrow-derived stromal cells (BMSCs) into contusion models of spinal cord injury (SCI). The authors used a high-throughput process to expand BMSCs and characterized them by flow cytometry, ELISA, and gene expression. They found that BMSCs secrete neurotrophic factors and cytokines with therapeutic potential for cell survival and axon growth. In adult immune-suppressed rats, mild, moderate, or severe contusions were generated using the MASCIS impactor. One week following injury, 0.5 to 1 x 106 BMSCs were injected into the lesioned spinal cord; control animals received vehicle injection. Biweekly behavioral tests included the Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB), exploratory rearing, grid walking, and thermal sensitivity. Animals receiving moderate contusions followed by BMSC grafts showed significant behavioral recovery in BBB and rearing tests when compared to controls. Animals receiving BMSC grafts after mild or severe contusion showed trends toward improved recovery. Immunocytochemistry identified numerous axons passing through the injury in animals with BMSC grafts but few in controls. BMSCS were detected at 2 weeks after transplantation; however, at 11 weeks very few grafted cells remained. The authors conclude that BMSCs show potential for repairing SCI. However, the use of carefully characterized BMSCs improved transplantation protocols ensuring BMSC, survival, and systematic motor and sensory behavioral testing to identify robust recovery is imperative for further improvement.

摘要

本研究评估了将人骨髓源性基质细胞(BMSCs)移植到脊髓损伤(SCI)挫伤模型后功能的恢复情况。作者采用高通量方法扩增BMSCs,并通过流式细胞术、酶联免疫吸附测定(ELISA)和基因表达对其进行表征。他们发现BMSCs分泌具有促进细胞存活和轴突生长治疗潜力的神经营养因子和细胞因子。在成年免疫抑制大鼠中,使用MASCIS撞击器造成轻度、中度或重度挫伤。损伤后一周,将0.5至1×10⁶个BMSCs注入受损脊髓;对照动物接受载体注射。每两周进行的行为测试包括巴索、比蒂和布雷斯纳汉运动评分量表(BBB)、探索性竖毛、网格行走和热敏感性测试。与对照组相比,接受中度挫伤后再进行BMSC移植的动物在BBB和竖毛测试中表现出显著的行为恢复。轻度或重度挫伤后接受BMSC移植的动物显示出恢复改善的趋势。免疫细胞化学鉴定出在接受BMSC移植的动物中,有许多轴突穿过损伤部位,而在对照组中则很少。移植后2周检测到BMSCs;然而,在11周时,残留的移植细胞很少。作者得出结论,BMSCs显示出修复SCI的潜力。然而,使用经过仔细表征的BMSCs、改进移植方案以确保BMSCs存活,以及进行系统的运动和感觉行为测试以确定显著的恢复情况,对于进一步改善至关重要。

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