Stem Cell-Derived Exosomes as Treatment for Stroke: a Systematic Review

Background The therapeutic potential of stem cells may largely be mediated by paracrine factors contained in exosomes released from intracellular endosomes. A systematic review was performed to identify the effects of stem cell-derived exosomes for their ability to induce restorative effects in animal models of stroke. Methods PubMed, Scopus, and ISI Web of Science databases were searched for all available articles testing stem cell-derived exosomes as therapeutic interventions in animal models of stroke until April 2020. The STAIR scale was used to assess the quality of the included studies. Results A total of 994 published articles were identified in the systematic search. After screening for eligibility, a total of 16 datasets were included. Type of cerebral ischemia was transient in majority studies and most studies used rat or mice adipose tissue-derived stem cells/bone marrow-derived stem cells. Eight studies indicated improved functional recovery while 8 were able to show reduced infarct volume as a result of exosome therapy. The beneficial effects were mainly attributed to reduced inflammation and oxidative stress, enhanced neurogenesis, angiogenesis, and neurite remodeling. Also, 4 studies demonstrated that exosomes hold great promise as an endogenous drug delivery nano-system. Conclusion In preclinical studies, use of stem cell-derived exosomes is strongly associated with improved neurological recovery and reduced brain infarct volume following stroke. Improved preclinical study quality in terms of treatment allocation reporting, randomization and blinding will accelerate needed progress towards clinical trials that should assess feasibility and safety of this therapeutic approach in humans. Graphical abstract