Exosomes derived from human placental mesenchymal stem cells in combination with hyperbaric oxygen therapy enhance neuroregeneration in a rat model of sciatic nerve crush injury
Fereshteh Talebpour Amiri, Aref Jafari, Fahimeh Ahmadi, Hossein Mokhtari, Amir Raoofi, Farshad Moharrami Kasmaie, Maryam Omran, Mohammad Amin Alimohammadi, Davood Nasiry
Abstract
Peripheral nerve damage continues to be a significant challenge in the field of medicine, with no currently available effective treatment. Currently, we investigated the beneficial effects of human placenta mesenchymal stem cells (PMSCs)- derived exosomes along with hyperbaric oxygen therapy (HBOT) in a sciatic nerve injury model. Seventy-five male mature Sprague-Dawley rats were allocated into five equal groups. In addition to the control group that received no intervention, damaged animals were allocated into four groups as follows: crush group, exosome group, HBOT group, and Exo+HBOT group. After the last neurological evaluations, tissue samples (sciatic nerve and dorsal root ganglion (DRG)) at the injury side, as well as spinal cord segments related to the sciatic nerve were collected to investigate histological, immunohistochemical, biochemical, and molecular characteristics. We found that the volume of the sciatic nerve, the thickness of the myelin sheath, the densities of nerve fibers and Schwann cells, the numerical densities of sensory neurons and glial cells in the DRG, as well as the numerical density of motor neurons in the anterior horn of the spinal cord, the levels of antioxidative factors (GSH, SOD, and CAT) in the sciatic nerve, as well as the neurological functions (EMG latency and SFI) in the treatment groups, especially the Exo+HBOT group, were significantly improved compared to the crush group. This is while the numerical density of glial cells in the spinal cord, the levels of an oxidative factor (MDA), and pro-inflammatory cytokines (IL-1β, TNF-α, and IFN- γ) considerably decreased in the treatment groups, particularly the Exo+HBOT group, compared to the crush group. We conclude that co-administration of PMSCs-derived exosomes and HBOT has synergistic neuroprotective effects in animals undergoing sciatic nerve injury. • We studied the effects of PMSCs - derived exosomes along with hyperbaric oxygen therapy following sciatic nerve injury. • Treatment improved histological changes in the sciatic nerve and related dorsal root ganglion, as well as anterior horn of spinal cord. • Treatment attenuated oxidative stress. • Treatment inhibited neuroinflammation. • Treatment improved rehabilitation of motor function.