Wang Jian, Yang Xun, Xu Miaomiao, Liu Hui, Liu Lijun, Tan Zhikai
College of Biology, Hunan University, Changsha, 410082, China.
Institute of Shenzhen, Hunan University Shenzhen, 518000, China.
Mater Today Bio. 2024 Mar 17;26:101033. doi: 10.1016/j.mtbio.2024.101033. eCollection 2024 Jun.
Regeneration of the architecturally complex blood vascular system requires precise temporal and spatial control of cell behaviours. Additional components must be integrated into the structure to achieve clinical success for in situ tissue engineering. Consequently, this study proposed a universal method for including any substrate type in vascular cell extracellular matrices (VCEM) via regulating selective adhesion to promote vascular tissue regeneration. The results uncovered that the VCEM worked as cell adhesion substrates, exhibited cell type specificity, and functioned as an address signal for recognition by vascular cells, which resulted in matching with the determined cells. The qPCR and immunofluorescence results revealed that a cell type-specific VCEM could be designed to promote or inhibit cell adhesion, consistenting with the expression patterns of eyes absent 3 (Eya3). In addition, a 3D vascular graft combined with VCEM which could recapitulate the vascular cell-like microenvironment was fabricated. The vascular graft revealed a prospective role for cellular microenvironment in the establishment of vascular cell distribution and tissue architecture, and potentiated the orderly regeneration and functional recovery of vascular tissues . The findings demonstrate that differential adhesion between cell types due to the cellular microenvironment is sufficient to drive the complex assembly of engineered blood vessel functional units, and underlies hierarchical organization during vascular regeneration.
结构复杂的血管系统的再生需要对细胞行为进行精确的时空控制。为了使原位组织工程取得临床成功，必须将其他成分整合到结构中。因此，本研究提出了一种通用方法，通过调节选择性黏附，将任何底物类型纳入血管细胞外基质（VCEM），以促进血管组织再生。结果发现，VCEM作为细胞黏附底物，表现出细胞类型特异性，并作为血管细胞识别的地址信号，从而与特定细胞相匹配。定量聚合酶链反应（qPCR）和免疫荧光结果显示，可以设计一种细胞类型特异性的VCEM来促进或抑制细胞黏附，这与无眼3（Eya3）的表达模式一致。此外，还制备了一种结合VCEM的三维血管移植物，该移植物可以模拟血管细胞样微环境。该血管移植物揭示了细胞微环境在建立血管细胞分布和组织结构方面的潜在作用，并促进了血管组织的有序再生和功能恢复。研究结果表明，细胞微环境导致的细胞类型之间的差异黏附足以驱动工程化血管功能单元的复杂组装，并构成血管再生过程中分层组织的基础。
