Brock John H, Graham Lori, Staufenberg Eileen, Collyer Eileen, Koffler Jacob, Tuszynski Mark H
1 Department of Neurosciences, University of California , San Diego, La Jolla, California.
2 Veterans Administration San Diego Healthcare System , La Jolla, California.
J Neurotrauma. 2016 Jun 15;33(12):1103-14. doi: 10.1089/neu.2015.4009. Epub 2015 Nov 13.
Bone marrow stromal cells (BMSCs) have been reported to exert potential neuroprotective properties in models of neurotrauma, although precise mechanisms underlying their benefits are poorly understood. Despite this lack of knowledge, several clinical trials have been initiated using these cells. To determine whether local mechanisms mediate BMSC neuroprotective actions, we grafted allogeneic BMSCs to sites of severe, compressive spinal cord injury (SCI) in Sprague-Dawley rats. Cells were administered 48 h after the original injury. Additional animals received allogeneic MSCs that were genetically modified to secrete brain-derived neurotrophic factor (BDNF) to further determine whether a locally administered neurotrophic factor provides or extends neuroprotection. When assessed 2 months post-injury in a clinically relevant model of severe SCI, BMSC grafts with or without BDNF secretion failed to improve motor outcomes. Thus, allogeneic grafts of BMSCs do not appear to act through local mechanisms, and future clinical trials that acutely deliver BMSCs to actual sites of injury within days are unlikely to be beneficial. Additional studies should address whether systemic administration of BMSCs alter outcomes from neurotrauma.
据报道，骨髓基质细胞（BMSCs）在神经创伤模型中具有潜在的神经保护特性，尽管其有益作用的精确机制尚不清楚。尽管缺乏相关知识，但已经开展了几项使用这些细胞的临床试验。为了确定局部机制是否介导BMSC的神经保护作用，我们将同种异体BMSCs移植到Sprague-Dawley大鼠严重压迫性脊髓损伤（SCI）部位。在原始损伤后48小时给予细胞。另外的动物接受经基因修饰以分泌脑源性神经营养因子（BDNF）的同种异体间充质干细胞，以进一步确定局部施用的神经营养因子是否提供或扩展神经保护作用。在严重SCI的临床相关模型中损伤后2个月进行评估时，分泌或不分泌BDNF的BMSC移植均未能改善运动结果。因此，BMSCs的同种异体移植似乎不是通过局部机制起作用，并且在数天内将BMSCs急性递送至实际损伤部位的未来临床试验不太可能有益。进一步的研究应探讨全身施用BMSCs是否会改变神经创伤的结果。
