miR-21 deficiency contributes to the impaired protective effects of obese rat mesenchymal stem cell-derived exosomes against spinal cord injury.

The therapeutic effect of stem cell transplantation in traumatic spinal cord injury (SCI) has been extensively studied these days, and evidence has shown that stem cell-derived exosomes and exosome-shuttled miRNA (e.g. miR-21) contribute to the protective effects of stem cell transplantation against SCI. It has been reported that obesity, a prevalent metabolic disorder, reshapes stem cells and their extracellular vesicles. However, the effects of exosomes derived from obese rat stem cells on SCI and its underlying mechanism remain unknown. Here, we examined the effects of exosomes derived from obese rat mesenchymal stem cells (MSCs) on SCI, and tested the role of miR-21 in their effects. We found that exosomes derived from obese rat MSCs showed decreased miR-21 levels and did not exert protective effects against SCI. Overexpression of miR-21 in obese rat MSCs restored the protective effects of exosomes purified from obese rat MSCs against SCI. In addition, obese rat MSCs showed insulin resistance, and MSC insulin resistance decreased miR-21 levels in its secreted exosomes. These results suggested that miR-21 deficiency in obese rat MSCs contributes to the impaired protective effects of obese rat MSCs-derived exosomes against SCI, and further reinforced the notion that miR-21 is a potential molecule for treatment of SCI.