DOI: 10.1002/ame2.70009
Transplanting neural stem cells overexpressing miRNA-21 can promote neural recovery after cerebral hemorrhage through the SOX2/LIN28-let-7 signaling pathway
Wei Dai1
Yongxia Li2
Jiarui Du1
Gang Shen1
Meimei Fan1
Zuopeng Su1
Fulin Xu1
Fang Yuan3
1.Department of Neurosurgery,Minhang Hospital,Fudan University,Shanghai,China2.Department of Emergency Medicine,Shanghai Jiao Tong University Affiliated Sixth People's Hospital,Shanghai,China3.Department of Neurosurgery,Shanghai Jiao Tong University Affiliated Sixth People's Hospital,Shanghai,China
摘要：Background:Intracerebral hemorrhage(ICH)remains a devastating neurological disorder with limited therapeutic options.Neural stem cell(NSC)-based therapies have emerged as a potential regenerative approach,yet the molecular mechanisms regulating NSC behavior require further elucidation.The role of miR-21 in NSC differentiation and proliferation during ICH recovery remains unexplored.
Methods:In vitro NSC cultures were analyzed for miR-21 expression dynamics dur-ing differentiation via qPCR.Lentiviral overexpression and knockdown of miR-21 were employed to assess its functional impact.The SOX2/LIN28-let-7 pathway was investigated using Western blot,luciferase reporter assays,and immunofluorescence.In vivo,miR-21-overexpressing NSCs were transplanted into a murine ICH model,with neurogenesis evaluated by immunostaining and neurological recovery assessed through behavioral tests(mNSS,rotarod).
Results:miR-21 expression significantly increased during NSC differentiation,correlating with reduced SOX2 levels.Mechanistically,miR-21 directly targeted SOX2,disrupting the SOX2/LIN28-let-7 axis to promote NSC proliferation and lineage commitment.In ICH mice,transplantation of miR-21-overexpressing NSCs enhanced neurogenesis and improved motor coordination and neurological deficits at 28days post-transplantation.
Conclusions:Our findings identify miR-21 as a critical regulator of NSC plasticity through SOX2/LIN28-let-7 signaling,highlighting its therapeutic potential for enhancing neuroregeneration and functional recovery in ICH.Targeting miR-21 may represent a novel strategy to optimize NSC-based therapies for hemorrhagic stroke.
机标关键词：mirna-21recoverythroughpathwaystemcellsaftercerebral
论文发表日期：2025-10-30
在线出版日期：2025-12-16（本平台首次上网日期，不代表文献的发表时间）
页数：15( 1760-1774 )
英文信息