4.8 Article

Biological nano agent produced by hypoxic preconditioning stem cell for stroke treatment

Journal

NANO RESEARCH
Volume 16, Issue 5, Pages 7413-7421

Publisher

TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-023-5470-z

Keywords

exosomes; hypoxia-preconditioning; stem cells; ischemic stroke; microenvironment

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Hypoxic preconditioning of neural stem cells (NSCs) can produce hypoxic exosomes, which can effectively treat ischemic stroke. These exosomes can target the injured brain and regulate the microenvironment to inhibit neuroinflammation and promote blood-brain barrier permeability recovery. Furthermore, they can also activate autologous NSCs and facilitate nerve regeneration. Hypoxic exosomes have therapeutic effects on both survival and behavioral outcomes in ischemic stroke mice.
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.

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