Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord

PLoS ONE, 2018 · DOI: https://doi.org/10.1371/journal.pone.0190358 · Published: January 2, 2018

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study investigates how intravenously delivered exosomes from mesenchymal stem cells (MSCexos) affect spinal cord injury (SCI) in rats. The MSCexos were found to target the injured area of the spinal cord, specifically M2 macrophages, which are associated with reducing inflammation. The researchers used fluorescently labeled MSCexos to track their location in the rats' bodies after SCI. They observed that the MSCexos accumulated in the injured spinal cord and the spleen, especially within M2 macrophages. The findings suggest that MSCexos may play a role in the therapeutic effects of MSCs on SCI recovery by influencing the activity of macrophages within the injured tissue.

Study Duration

Not specified

Participants

Adult male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
IV delivered MSCexos traffic to contusive SCI sites but not uninjured spinal cord tissue.
2
MSCexos are specifically taken up by M2 macrophages, and not M1 macrophages, at the SCI site.
3
The hotspots of DiR fluorescence within CD206+ M2-type macrophages strongly co-localized with staining for the characteristic exosome antigen CD63.

Research Summary

This study investigated the distribution and cellular targeting of intravenously infused MSCexos in rats with SCI. The MSCexos were detected in the contused regions of the spinal cord and the spleen. DiR “hotspots” were specifically associated with CD206-expressing M2 macrophages in the spinal cord. This was confirmed by co-localization with anti-CD63 antibodies labeling a tetraspanin characteristically expressed on exosomes. The findings suggest that extracellular vesicles released by MSCs may mediate some therapeutic effects of IV MSC administration on spinal cord injury recovery by regulating the actions of macrophages within the lesion.

Practical Implications

Targeted Therapy

MSCexos can be used as a targeted therapy for SCI by delivering therapeutic agents directly to M2 macrophages at the injury site.

Immune Modulation

MSCexos can modulate the immune response after SCI, potentially reducing inflammation and promoting tissue repair.

Drug Delivery

MSCexos can be utilized as a novel drug delivery system for SCI, encapsulating and delivering therapeutic molecules to specific cells in the injured spinal cord.

Study Limitations

1
The number of animals transplanted with MSCexos was relatively small.
2
The effect of MSCexos uptake on macrophage function is uncertain.
3
It is unclear whether the actions of DiR-MSCexos on spinal cord injury are due solely, or even primarily, to effects on macrophages.

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