2. Academic Validation
  3. Clinically Inspired Multimodal Treatment Using Induced Neural Stem Cells-Derived Exosomes Promotes Recovery of Traumatic Brain Injury through Microglial Modulation

Clinically Inspired Multimodal Treatment Using Induced Neural Stem Cells-Derived Exosomes Promotes Recovery of Traumatic Brain Injury through Microglial Modulation

  • Adv Sci (Weinh). 2025 Sep 24:e08574. doi: 10.1002/advs.202508574.
Jiaojiao Li 1 2,  Maoxiang Xu 1 2,  Boyu Cai 1 2,  Xiangyu Li 3,  Zhanping Liang 3,  Xiaohuan Xia 3,  Haitao Zhang 4,  Zhiwen Zhang 5,  Fei Tan 1 2 6,  Jialin Charlie Zheng 3 7
Affiliations

Affiliations

  • 1 Department of ORL-HNS, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200434, China.
  • 2 Plasma Medicine and Surgical Implants Center, Tongji University School of Medicine, Shanghai, 200092, China.
  • 3 Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200092, China.
  • 4 Department of Neurosurgery, the Fourth Medical Center of PLA General Hospital, Beijing, 100048, China.
  • 5 Department of Neurosurgery, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200434, China.
  • 6 Department of ORL-HNS, The Royal College of Surgeons of England, London, WC2A3PE, UK.
  • 7 Shanghai Frontiers Science Center of Nanocatalytic Medicine, Tongji University, Shanghai, 200331, China.
PMID: 40990055 DOI: 10.1002/advs.202508574
Abstract

Traumatic brain injury (TBI) poses serious physical, psychosocial, and economic threats to millions of patients globally each year. While current treatment options, primarily surgery and medication, vary with TBI severity, there is no universal therapeutic agent applicable in both surgical and medical contexts. In the present study, exosomes derived from induced neural stem cells (iNSC-Exo) as a versatile therapeutic agent for TBI are investigated using a preclinical murine model. The iNSC-Exo treatment is found to exert therapeutic effects by mediating anti-neuroinflammation and neuroprotection, thereby promoting functional and cognitive recovery in TBI mice. Besides, two clinically inspired administration modalities are established for iNSC-Exo: local delivery and systemic delivery. Their efficacy is enhanced via a novel injectable hydrogel and RVG targeting for systemic delivery, respectively. Finally, the unprecedented single-cell characterization of mouse brain tissue, both pre- and post-iNSC-Exo treatment, confirms that microglia represent the predominant type of cells affected. Two microglial subpopulations (i.e., Microglia_Nrg3 and Microglia_Rarb) are identified with a reduced state of differentiation, and their connectivity with neurons is predicted through activation of the NRXN signaling pathway. Overall, these findings demonstrated that iNSC-Exo offers a versatile and potent treatment platform with clinical potential for TBI management.

Keywords

exosomes; induced neural stem cells; injectable hydrogel; targeted delivery; traumatic brain injury.

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