State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Cell Prolif. 2019 Mar;52(2):e12557. doi: 10.1111/cpr.12557. Epub 2018 Nov 28.
The aim of the study was to investigate the effect of matrix stiffness on arteriovenous differentiation of endothelial progenitor cells (EPCs) during vasculogenesis in nude mice.
Dextran hydrogels of differing stiffnesses were first prepared by controlling the crosslinking reaction to generate different thioether bonds. Hydrogels with stiffnesses matching those of the arterial extracellular matrix and venous extracellular matrix were separately combined with mouse bone marrow-derived EPCs and subcutaneously implanted on either side of the backs of nude mice. After 14 days, artery-specific marker Efnb2 and vein-specific marker Ephb4 in the neovasculature were detected to determine the effect of matrix stiffness on the arteriovenous differentiation of EPCs in vivo.
Fourteen days after the implantation of the EPC-loaded dextran hydrogels, new blood vessels were observed in both types of hydrogels. We further verified that matrix stiffness regulated the arteriovenous differentiation of EPCs during vasculogenesis via the Ras/Mek pathway.
Matrix stiffness regulates the arteriovenous differentiation of EPCs during vasculogenesis in nude mice through the Ras/Mek pathway.
本研究旨在探讨在裸鼠血管生成过程中，基质刚度对内皮祖细胞（EPC）向动静脉分化的影响。
首先通过控制交联反应来制备不同硬度的葡聚糖水凝胶，以生成不同的硫醚键。将硬度与动脉细胞外基质和静脉细胞外基质相匹配的水凝胶分别与小鼠骨髓来源的 EPC 结合，并皮下植入裸鼠背部两侧。14 天后，检测新血管中动脉特异性标记物 Efnb2 和静脉特异性标记物 Ephb4，以确定基质刚度对体内 EPC 动静脉分化的影响。
植入负载 EPC 的葡聚糖水凝胶 14 天后，两种水凝胶中均观察到新生血管。我们进一步证实，基质刚度通过 Ras/Mek 通路调节血管生成过程中 EPC 的动静脉分化。
基质刚度通过 Ras/Mek 通路调节裸鼠血管生成过程中 EPC 的动静脉分化。
