Crosstalk between PC 12 cells and endothelial cells in an artificial neurovascular niche constructed by a dual-functionalized selfassembling peptide nanofiber hydrogel  

作　　者：Zhe Zhang Yi Chai He Zhao Shuhui Yang Wei Liu Zihui Yang Weilong Ye Chenlong Wang Xiaohan Gao Xiangdong Kong Xiaodan Sun Lingyun Zhao Tuoyu Chen Yuqi Zhang Jiaju Lu Xiumei Wang 

机构地区：[1]State Key Laboratory of New Ceramics and Fine Processing,School of Materials Science and Engineering,Tsinghua University,Beijing 100084,China [2]Department of Neurosurgery,Yuquan Hospital,School of Clinical Medicine,Tsinghua University,Beijing 100084,China [3]Institute of Smart Biomedical Materials,School of Materials Science and Engineering,Zhejiang Sci-Tech University,Hangzhou 310018,China [4]Department of orthopedics,Dongzhimen hospital,Beijing University of Chinese Medicine,Beijing 100700,China [5]Department of Neurosurgery,The First Hospital of Hebei Medical University,Shijiazhuang 050000,China [6]Department of Obstetrics and Gynecology,Beijing Tsinghua Changgung Hospital,Beijing 102218,China [7]Department of Chemistry,Tsinghua University,Beijing 100084,China

出　　处：《Nano Research》2022年第2期1433-1445,共13页纳米研究（英文版）

基　　金：support from the National Key R&D Program of China(Nos.2020YFC1107600 and 2018YFB0704304);the National Natural Science Foundation of China(Nos.31771056 and 31771052);Shandong Province Key R&D Program of China(No.2019JZZY011106).

摘　　要：The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention.Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials.In this study,we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ(RGI)and KLTWQELYQLKYKGI(KLT)to construct an artificial neurovascular microenvironment.The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma(PC12)cells and tube-like structures formation of human umbilical vein endothelial cells(HUVECs)in vitro,and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model.Using indirect co-culture models,we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs.When the two cells types were directly co-cultured on the dua卜functionalized peptide hydrogel,the efficiency of cell-cell communication was enhanced,which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology,and HUVECs tube-like structure formation.In summary,the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.

关 键 词：neurovascular microenvironment self-assembling peptide CO-CULTURE nanofiber hydrogel brain injury 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]