Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, Florida, United States of America.
PLoS One. 2013 Sep 4;8(9):e74857. doi: 10.1371/journal.pone.0074857. eCollection 2013.
Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.
在这里,我们报告了一种干细胞在修复创伤性脑损伤中的独特作用机制,即它们能够利用神经发生龛和损伤脑区之间的生物桥。这种生物桥通过免疫组织化学和激光捕获可视化,对应于神经发生室下区和损伤皮质之间的区域。生物桥表达高水平的细胞外基质金属蛋白酶,最初由一波移植的干细胞表达,但随后仅包含少量或无法检测到的移植物,并被新形成的宿主细胞过度生长,这暗示了干细胞的一种新特性。移植的干细胞表现为宿主神经发生细胞迁移的运输途径,但一旦在神经发生区和损伤脑区之间形成生物桥,移植的细胞就会消失,并将其任务交给宿主神经发生细胞。我们的发现表明,宿主细胞可以通过作为内源性修复机制启动的生物桥从神经发生龛长距离迁移到损伤脑区。这是首例报道的干细胞铺就的“生物桥”。事实上,迄今为止,干细胞修复机制的两个主要学派主要支持“细胞替代”的概念和“营养因子分泌”的旁观者效应。本研究首次观察到干细胞诱使宿主细胞参与脑修复,这推进了干细胞生物学和细胞外基质的基础科学概念,并激发了将这种干细胞铺就的生物桥从细胞替代和营养因子分泌推广到创伤性脑损伤和其他神经疾病治疗的转化研究。