Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Sanbio Inc., Mountain View CA, USA.
Front Syst Neurosci. 2014 Jun 24;8:116. doi: 10.3389/fnsys.2014.00116. eCollection 2014.
Modified mesenchymal stromal cells (MSCs) display a unique mechanism of action during the repair phase of traumatic brain injury by exhibiting the ability to build a biobridge between the neurogenic niche and the site of injury. Immunohistochemistry and laser capture assay have visualized this biobridge in the area between the neurogenic subventricular zone and the injured cortex. This biobridge expresses high levels of extracellular matrix metalloproteinases (MMPs), which are initially co-localized with a stream of transplanted MSCs, but later this region contains only few to non-detectable grafts and becomes overgrown by newly recruited host cells. We have reported that long-distance migration of host cells from the neurogenic niche to the injured brain site can be attained via these transplanted stem cell-paved biobridges, which serve as a key regenerative process for the initiation of endogenous repair mechanisms. Thus, far the two major schools of discipline in stem cell repair mechanisms support the idea of "cell replacement" and the bystander effects of "trophic factor secretion." Our novel observation of stem cell-paved biobridges as pathways for directed migration of host cells from neurogenic niche toward the injured brain site adds another mode of action underlying stem cell therapy. More in-depth investigations on graft-host interaction will likely aid translational research focused on advancing this stem cell-paved biobridge from its current place, as an equally potent repair mechanism as cell replacement and trophic factor secretion, into a new treatment strategy for traumatic brain injury and other neurological disorders.
经修饰的间充质基质细胞（MSCs）在创伤性脑损伤的修复阶段表现出独特的作用机制，能够在神经发生龛与损伤部位之间建立生物桥。免疫组织化学和激光捕获分析已经在神经发生室下区和损伤皮质之间的区域可视化了这种生物桥。该生物桥表达高水平的细胞外基质金属蛋白酶（MMPs），最初与移植的 MSC 流共定位，但后来该区域仅包含少量或无法检测到的移植物，并被新募集的宿主细胞所覆盖。我们已经报道，通过这些移植的干细胞铺成的生物桥，可以实现宿主细胞从神经发生龛向损伤大脑部位的远距离迁移，这是启动内源性修复机制的关键再生过程。到目前为止，干细胞修复机制的两个主要学派都支持“细胞替代”和“营养因子分泌的旁观者效应”的观点。我们对干细胞铺成的生物桥作为宿主细胞从神经发生龛向损伤大脑部位定向迁移途径的新观察结果，为干细胞治疗增加了另一种作用机制。对移植物-宿主相互作用的更深入研究可能有助于转化研究，将这种干细胞铺成的生物桥从目前作为与细胞替代和营养因子分泌同等有效修复机制的位置推进到创伤性脑损伤和其他神经障碍的新治疗策略。
