Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel wi...Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.展开更多
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 ne...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.展开更多
基金This study was partly funded by grants from the National Natural Science Funding of China(82172424,82271629)Outstanding Youth Fund of Zhejiang Province(LR22H060002)+2 种基金Zhejiang Medical and Health Science and Technology Plan Project(2022RC210,2021KY212)Wenzhou Basic Science Research Plan Project(Y20210045)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028).
文摘Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.
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).
文摘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.