1. Human-Derived Induced GABAergic Progenitor Cells Improve Cognitive Function in Mice and Inhibit Astrocyte Activation with Anti-Inflammatory Exosomes.
- Author
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Chen C, Lan Z, Tang X, Chen W, Zhou X, Su H, Su R, Chen Z, Chen H, Guo Y, and Deng W
- Subjects
- Animals, Mice, Humans, Alzheimer Disease metabolism, Mice, Transgenic, Cognition physiology, Male, Exosomes transplantation, Exosomes metabolism, Astrocytes metabolism, GABAergic Neurons metabolism, Neural Stem Cells transplantation, Neural Stem Cells metabolism
- Abstract
Objective: The role of gamma-aminobutyric acid-ergic (GABAergic) neuron impairment in Alzheimer's disease (AD), and if and how transplantation of healthy GABAergic neurons can improve AD, remain unknown., Methods: Human-derived medial ganglionic eminence progenitors (hiMGEs) differentiated from programmed induced neural precursor cells (hiNPCs) were injected into the dentate gyrus region of the hippocampus (HIP)., Results: We showed that grafts migrate to the whole brain and form functional synaptic connections in amyloid precursor protein gene/ presenilin-1 (APP/PS1) chimeric mice. Following transplantation of hiMGEs, behavioral deficits and AD-related pathology were alleviated and defective neurons were repaired. Notably, exosomes secreted from hiMGEs, which are rich in anti-inflammatory miRNA, inhibited astrocyte activation invitro and in vivo, and the mechanism was related to regulation of CD4
+ Th1 cells mediated tumor necrosis factor (TNF) pathway., Interpretation: Taken together, these findings support the hypothesis that hiMGEs transplantation is an alternative treatment for neuronal loss in AD and demonstrate that exosomes with anti-inflammatory activity derived from hiMGEs are important factors for graft survival. ANN NEUROL 2024;96:488-507., (© 2024 American Neurological Association.)- Published
- 2024
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