Abstract
Background:
Recent preclinical studies of stroke recovery have explored the possibility of utilizing exosomes (ES) instead of complete cells as therapeutic agents. ES are endosomal origin small-membrane vesicles with a size of 40 to 100nm in diameter, secreted from many types of cells including mesenchymal stem cells (MSCs). ES-encapsulated transfer of miRNAs promotes neurite remodeling and functional recovery of stroke in rats. The optimal route of delivery of ES in stroke is not established. While a few studies have shown efficacy of intra-venous exosomes administration for stroke, there is one study exploring intra-arterial exosome therapy (IAX) with single dose of 100ug exosomes. We propose intra-arterial delivery of exosomes in a dose escalation study to establish safety and early efficacy.
Methods:
Female ovariectomized Sprague-Dawley rats were exposed to MCAo for 90 min. Rats were treated with IAX (10, 50 and 100ug/0.5mL), IAMSCs (1x10
5
cells/0.5mL) or IA phosphate-buffered saline (IAPBS) at 1 day (1D) after MCAo. To test neurological and motor function, the standardized neurobehavioral test battery and the rotarod test were performed. The mean duration (in seconds) on the device was recorded from 3 rotarod measurements. The rats were tested at pre-surgery, 7, 15 and 30 days post-MCAo.
Results:
There was no neurological worsening or mortality post IA exosome delivery at any dose tier. The Neurological deficit score of IAX 10ug treatment group at POD 7, 15 and 30, and IAX 50ug treatment at POD 15 were significantly improved in comparison to IA PBS. IAX 10ug treatment group showed trend of improvement in motor coordination compared to the IA PBS/MSC/higher doses of exosome treatment groups.
Conclusions:
The Neurological deficit scores of IAX 10ug treatment group were significantly improved in comparison to IA PBS. Lower dose than previously published might be most effective, and noninferior to IA-MSCs.