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脊髓内细胞移植注射技术。临床和转化的考虑。

Technical aspects of spinal cord injections for cell transplantation. Clinical and translational considerations.

机构信息

The Miami Project To Cure Paralysis, University of Miami, FL, USA.

出版信息

Brain Res Bull. 2011 Mar 10;84(4-5):267-79. doi: 10.1016/j.brainresbull.2010.11.007. Epub 2010 Nov 16.

DOI:10.1016/j.brainresbull.2010.11.007
PMID:21087657
Abstract

Spinal cord injections may be used to transplant cellular suspensions for the experimental treatment of spinal cord injury. These injections cause some additional injury due to needle penetration, spinal cord motion during injection, creation of intraparenchymal pressure gradients and hydrodynamic dissection, instillation of a deforming cell mass and possible cord ischemia. It is important to understand these variables to maximize the safety of injections and avoid injury to spared structures. Surprisingly little knowledge exists regarding these variables. Further complicating spinal cord injections is the fact that intraparenchymal events are not evident during injections. As cell injections for spinal cord injury enter extensive clinical testing it is important to both optimize the procedures, and reduce the probability of technical failures. In this review current knowledge and key areas for knowledge advance are identified. These include a need for a more thorough understanding of how the spinal cord is affected by needle entry and dwell, needle-cord relative motion, instillation of highly concentrated cellular volumes, compliance of intact and damaged spinal cord tissue, radial tensile stresses and hydrodynamic forces created by injection, and the rates of pressure gradient dissipation in damaged and intact tissue. We propose that if the variables associated with injury can be identified, injection injury may be reduced and we illustrate the use of ultrasound to monitor injection in a spinal cord model. We also suggest that injectate backout or extrusion be reinterpreted as a clear indicator of excessive intraparenchymal pressure. The strengths and weaknesses of alternatives to direct intraparenchymal injection are also discussed.

摘要

脊髓内注射可用于移植细胞悬浮液,以治疗脊髓损伤。这些注射会因针穿透、注射过程中脊髓运动、脑实质内压力梯度和流体动力学分离、变形细胞团的灌输以及可能的脊髓缺血而造成额外的损伤。了解这些变量对于最大限度地提高注射安全性和避免损伤保留结构非常重要。然而,关于这些变量的知识却很少。使脊髓内注射变得更加复杂的是,脑实质内的事件在注射过程中并不明显。由于细胞注射治疗脊髓损伤正在进入广泛的临床测试,因此优化这些程序并降低技术故障的概率非常重要。在这篇综述中,确定了当前的知识和知识进展的关键领域。这些领域包括需要更深入地了解针进入和停留、针与脊髓的相对运动、高浓度细胞体积的灌输、完整和受损脊髓组织的顺应性、注射产生的径向拉伸应力和流体动力、以及在受损和完整组织中压力梯度消散的速度等因素如何影响脊髓。我们假设,如果能够识别与损伤相关的变量,那么注射损伤可能会减少,并举例说明了如何在脊髓模型中使用超声监测注射。我们还建议将回抽或挤出的注射剂重新解释为脑实质内压力过高的明确指标。此外,还讨论了直接脑实质内注射的替代方法的优缺点。

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