Exosomes make a significant contribution during stem cell-based therapy due to the abundant contents.Accumulating evidence implies exosomes can act as potential biological nano agents.We herein propose hypoxic precond...Exosomes make a significant contribution during stem cell-based therapy due to the abundant contents.Accumulating evidence implies exosomes can act as potential biological nano agents.We herein propose hypoxic preconditioning for neural stem cells(NSCs)that could produce hypoxic exosomes for efficient treatment of ischemic stroke.Hypoxic preconditioning on NSCs significantly altered the miRNAs encapsulated in exosomes.Notably,hypoxic exosomes could target the injured brain to regulate the microenvironment to inhibit neuroinflammation and promote blood–brain barrier permeability recovery.Additionally,the autologous NSCs in Nestin-CreER mice could be activated by hypoxic exosomes to facilitate nerve regeneration.After hypoxic preconditioning,exosomes further exerted therapeutic effects on both survival(25%)and behavioral outcomes in ischemic stroke mice.Overall,hypoxic preconditioning NSCs can produce effective nano agent and may represent a promising strategy for clinical neurorestorative therapy.展开更多
基金the National Natural Science Foundation of China(Nos.U22A20383 and 82003668)the Natural Science Foundation of Zhejiang Province(Nos.LD22H300002 and LQ21H300002)+2 种基金China Postdoctoral Science Foundation(No.2020M671771)Ningbo Technology Innovation 2025 Major Special Project(No.2022Z150)the innovative team of acupuncture and Chinese herbal medicine for prevention and treatment of senile neurodegenerative diseases.
文摘Exosomes make a significant contribution during stem cell-based therapy due to the abundant contents.Accumulating evidence implies exosomes can act as potential biological nano agents.We herein propose hypoxic preconditioning for neural stem cells(NSCs)that could produce hypoxic exosomes for efficient treatment of ischemic stroke.Hypoxic preconditioning on NSCs significantly altered the miRNAs encapsulated in exosomes.Notably,hypoxic exosomes could target the injured brain to regulate the microenvironment to inhibit neuroinflammation and promote blood–brain barrier permeability recovery.Additionally,the autologous NSCs in Nestin-CreER mice could be activated by hypoxic exosomes to facilitate nerve regeneration.After hypoxic preconditioning,exosomes further exerted therapeutic effects on both survival(25%)and behavioral outcomes in ischemic stroke mice.Overall,hypoxic preconditioning NSCs can produce effective nano agent and may represent a promising strategy for clinical neurorestorative therapy.
