Baranes D, Cove J, Blinder P, Shany B, Peretz H, Vago R
Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Tissue Eng. 2007 Mar;13(3):473-82. doi: 10.1089/ten.2006.0052.
Identifying scaffolds supporting in vitro reconstruction of active neuronal tissues in their 3-dimensional (3D) conformation is a major challenge in tissue engineering. We have previously shown that aragonite coral exoskeletons support the development of neuronal tissue from hippocampal neurons and astrocytes. Here we show for the first time that the porous aragonite skeleton obtained from bio-fabricated hydrozoan Millepora dichotoma supports the spontaneous organization of dissociated hippocampal cells into highly interconnected 3D ganglion-like tissue formations. The ganglion-like cell spheres expanded hundreds of microns across and included hundreds to thousands of astrocytes and mature neurons, most of them having only cell-cell and no cell-surface interactions. The spheres were linked to the surface directly or through a neck of cells and were interconnected through thick bundles of dendrites, varicosity-bearing axons, and astrocytic processes. Thus, M. dichotoma exoskeleton is a novel scaffold with the unprecedented ability to support a highly ordered organization of neuronal tissue. This unexpected organization opens new opportunities for neuronal tissue regeneration, because the spheres resemble in vivo nervous tissue having high volume of cells associated primarily through cell-cell rather than cell-matrix interactions.
识别能够支持活性神经元组织以三维（3D）构象进行体外重建的支架是组织工程中的一项重大挑战。我们之前已经表明，文石珊瑚外骨骼能够支持海马神经元和星形胶质细胞发育成神经元组织。在此，我们首次展示了从生物制造的水螅虫二叉千孔螅获得的多孔文石骨架能够支持解离的海马细胞自发组织成高度互连的3D神经节样组织结构。这种神经节样细胞球直径扩展到数百微米，包含数百到数千个星形胶质细胞和成熟神经元，其中大多数仅存在细胞 - 细胞间相互作用，而没有细胞 - 表面相互作用。这些细胞球直接或通过细胞颈部与表面相连，并通过厚厚的树突束、有曲张体的轴突和星形胶质细胞突起相互连接。因此，二叉千孔螅外骨骼是一种新型支架，具有支持神经元组织高度有序组织的前所未有的能力。这种意想不到的组织结构为神经元组织再生带来了新的机遇，因为这些细胞球类似于体内神经组织，其中大量细胞主要通过细胞 - 细胞而非细胞 - 基质相互作用关联在一起。
