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Updated: Dec 31, 2025
Transplantation of Human Induced Pluripotent Stem Cell-Derived Microglia in Immunocompetent Mice Brain via Non-Invasive Transnasal Route
Published on: May 31, 2022
Intranasally Administered Human MSC-Derived Extracellular Vesicles Pervasively Incorporate into Neurons and Microglia
Maheedhar Kodali1, Olagide W Castro2, Dong-Ki Kim1
1Institute for Regenerative Medicine, Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, 1114 TAMU, College Station, TX 77842, USA.
Intranasal administration of human mesenchymal stem cell-derived extracellular vesicles (EVs) effectively delivers them to both sides of the brain. Neuronal uptake of these EVs increases in injured areas, suggesting injury signals may enhance EV targeting for neurodegenerative disease therapy.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Cell Biology
Background:
- Human bone marrow mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) show therapeutic potential for neurological disorders due to anti-inflammatory and neuroprotective effects.
- Intranasal (IN) administration offers a non-invasive route for EV delivery to the brain, reaching multiple regions quickly.
Purpose of the Study:
- To investigate the distribution and cellular uptake of IN-administered hMSC-EVs in intact and injured rat brains.
- To determine if brain injury influences EV entry into different neural cell types.
Main Methods:
- PKH26-labeled hMSC-EVs were administered intranasally to naive rats and rats with kainate-induced status epilepticus (SE).
- EV distribution and incorporation into neurons and microglia were quantified in various forebrain regions using confocal microscopy six hours post-administration.
Main Results:
- IN-administered EVs were detected bilaterally in most forebrain regions in both intact and SE-injured rats.
- Neuronal EV uptake was significantly higher in the hippocampal CA1 and entorhinal cortex of SE-injured rats compared to naive rats.
- Microglial EV uptake remained consistent across all measured regions, regardless of brain injury status.
Conclusions:
- Unilateral IN administration of hMSC-EVs facilitates efficient bilateral delivery to neurons and microglia in the brain.
- Increased neuronal EV uptake in injured brain regions suggests that injury-related signals enhance EV targeting, offering a promising strategy for treating neurodegenerative diseases.
