National Research Center Kurchatov Institute, Moscow, 123098, Russian Federation.
Priorov Federal Scientific Research Institute of Traumatology and Orthopedics, Moscow, 127299, Russian Federation.
Cell Biol Int. 2019 Oct;43(10):1193-1200. doi: 10.1002/cbin.11112. Epub 2019 Jul 16.
It is a well-known fact, that there is a close interconnection between vascular and neural structures in both embryonic development and postnatal life. Different models have been employed to dissect the mechanisms of these interactions, ranging from in vitro systems (e.g., co-culture of neural and endothelial cells) to in vivo imaging of central neural system recovery in laboratory animals after artificially induced trauma. Nevertheless, most of these models have serious limitations. Here, we describe an ex vivo model, representing an organotypic co-culture of aortic fragments (AF) with longitudinal slices of mouse neonatal spinal cord (SC) or dorsal root ganglia (DRG). The samples were co-cultured in a medium adapted for SC tissue and lacking any pro-angiogenic or neurotrophic growth factors. It was found, that cultivation of AFs in the SC injury zone (transversal dissection of a SC slice) resulted in the initiation of active aortic sprouting. Remarkably, the endothelial cells exiting the AFs never invaded the SC tissue, concentrating in a nearby area (negative taxis). In contrast, the DRGs, while also promoting the sprouting, were a target of active endothelial CD31 cell invasion (positive taxis). Thus, the tissues of both central and peripheral nervous systems have a prominent positive effect on aortic sprouting, while the vector of endothelial cell expansion is strictly nervous-tissue-type dependent. The ex vivo AF co-culture with SC or DRG appeared to be a useful and promising model for a further endeavor into the mechanisms driving the complex interactions between neural and endothelial tissues.
这是一个众所周知的事实，即血管和神经结构在胚胎发育和出生后生活中有着密切的相互联系。为了剖析这些相互作用的机制，人们采用了不同的模型，从体外系统（例如，神经和内皮细胞的共培养）到实验室动物中枢神经系统在人工诱导损伤后恢复的体内成像。然而，大多数这些模型都有严重的局限性。在这里，我们描述了一种离体模型，代表了主动脉片段（AF）与新生小鼠脊髓（SC）或背根神经节（DRG）的纵切片的器官型共培养。将样本在适应 SC 组织的培养基中共同培养，且培养基中不含有任何促血管生成或神经营养生长因子。研究发现，在 SC 损伤区（SC 切片的横切）中培养 AF 会引发主动的主动脉出芽。值得注意的是，从 AF 中伸出的内皮细胞从未侵入 SC 组织，而是集中在附近区域（负趋化性）。相比之下，DRG 虽然也促进了出芽，但却是内皮细胞 CD31 细胞侵袭的活跃靶点（正趋化性）。因此，中枢和周围神经系统的组织对主动脉出芽有显著的积极影响，而内皮细胞扩展的载体则严格依赖于神经组织类型。AF 与 SC 或 DRG 的离体共培养似乎是一种有用且有前途的模型，可以进一步深入研究驱动神经和内皮组织之间复杂相互作用的机制。
