Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats  

作　　者：Sipin Zhu Yibo Ying Yan He Xingxing Zhong Jiahui Ye Zhiyang Huang Min Chen Qiuji Wu Yifan Zhang Ziyue Xiang Yurong Tu Weiyang Ying Jian Xiao Xiaokun Li Qingsong Ye Zhouguang Wang 

机构地区：[1]Department of Orthopaedics,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,325000,China [2]Molecular Pharmacology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,Zhejiang,China [3]Department of Pain Medicine,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou,325000,Zhejiang,China [4]School and Hospital of Stomatology,Wenzhou Medical University,Wenzhou,325035,China [5]Laboratory of Regenerative Medicine,Tianyou Hospital,Wuhan University of Science and Technology,Wuhan,430064,China [6]The Department of Cardiology,The First Affiliated Hospital,School of Medicine,Zhejiang University,China [7]Massachusetts General Hospital,Harvard University,Boston,02114,USA [8]Research Units of Clinical Translation of Cell Growth Factors and Diseases Research,Chinese Academy of Medical Science,China [9]Center of Regenerative Medicine,Renmin Hospital of Wuhan University,Wuhan,630060,China

出　　处：《Bioactive Materials》2021年第8期2452-2466,共15页生物活性材料（英文）

基　　金：This study was partly funded by a grant the National Natural Science Foundation of China(81802235,81871503),Zhejiang Medical and Health Science and Technology Plan Project(2021KY212),and Wenzhou Basic Science Research Plan Project(Y2020050),Advanced Postdoctoral Programs of Zhejiang(zj2019030),China Postdoctoral Science Foundation(2019M662015),CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028).

摘　　要：Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.

关 键 词：Spinal cord injury Adeno-associated virus Basic fibroblast growth factor Dental pulp stem cell Vascular regulation Hypoxic microenvironment 

分 类 号：R318[医药卫生—生物医学工程]