Department of Oral Implantology, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
J Cell Physiol. 2023 Sep;238(9):2135-2146. doi: 10.1002/jcp.31074. Epub 2023 Aug 10.
One of the major obstacles to the effective application of vascularized fruit is an insufficient understanding of the relationship between the microenvironment and neovascular homeostasis. The role of extracellular matrix stiffness in regulating the structural and functional stability of neovascularization has not yet been elucidated. This study explored the effects of matrix stiffness on neovascular homeostasis in nude mice. Dextran hydrogels with three different stiffnesses were separately combined with mouse bone marrow-derived endothelial progenitor cells (EPCs) and subcutaneously implanted into the backs of nude mice. After 14 days, neovascular homeostasis indicators in the different groups were measured. Cell autophagy levels were evaluated, and inhibitor assays were performed to explore the underlying mechanism. New blood vessels were generated in the three stiffnesses of the EPC-loaded dextran hydrogels 14 days after implantation. The newly formed vessels tended to have better structural stability in softer hydrogels. Endothelial function markers, such as endothelial nitric oxide synthase and E-selectin, were downregulated as the matrix stiffness increased. Furthermore, we found that cell autophagy levels decreased in stiffer matrices, and autophagy inhibition attenuated neovascular homeostasis. A soft matrix is conducive to maintaining neovascular homeostasis through autophagy in nude mice.
血管化水果的有效应用面临的主要障碍之一是对微环境与新血管稳态之间关系的认识不足。细胞外基质硬度在调节新血管生成的结构和功能稳定性方面的作用尚未阐明。本研究探讨了基质硬度对裸鼠新血管稳态的影响。分别将三种不同硬度的葡聚糖水凝胶与小鼠骨髓源性内皮祖细胞（EPC）结合，并皮下植入裸鼠背部。14 天后，测量各组的新血管稳态指标。评估细胞自噬水平，并进行抑制剂实验以探讨潜在机制。植入后 14 天，负载 EPC 的葡聚糖水凝胶的三种硬度均产生新血管。在较软的水凝胶中，新形成的血管结构稳定性更好。随着基质硬度的增加，内皮功能标志物，如内皮型一氧化氮合酶和 E-选择素的表达下调。此外，我们发现，在较硬的基质中细胞自噬水平降低，自噬抑制减弱了新血管稳态。在裸鼠中，软基质通过自噬有利于维持新血管稳态。
