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Description
Spinal cord Injury (SCI) is a life changing event with a high number of new cases reported every year. The most common cause of SCI comes from traumatic events, such as traffic accidents, falls, violence and sports activities, while the non-traumatic events (tumours, neurodegenerative and infectious diseases) are less prevalent. The injury incurred in the spinal cord tissue triggers several pathophysiological events which cause damage and supress axonal growth in the spinal cord tissue. These events consist of activation of apoptotic pathways, the release of inflammatory cytokines and the formation of a glial scar that primarily contains further damage, but also releases biomolecules that inhibit axons outgrowth. It affects nerve fibres passing through the lesion site causing motor dysfunction and altered sensation, causing incapacitating conditions to SCI patients. In this work we suggest a new multidisciplinary approach, combining the value of Adipose Tissue Derived Stem Cells (ASCs) secretome and Electrical epidural stimulation (EES). ASCs secretome was reported to promote regaining of function after SCI in a mouse model, likely promoted by the factors present in it which include anti-apoptotic and angiogenic factors, neuroprotectants and immunomodulators which may prime the unfavourable environment created upon SCI to a more neuroprotective/regenerative one. These benefits combined with the EES, which promote spinal cord plasticity, central pattern generator activation and stepping initiation is expected to improve functional gains after SCI. In an organotypic model of ex vivo spinal cord, we have observed that the secretome from ASCs is a potent modulator of axonal growth and inflammatory cells migration. We observed an increase in neurite outgrowth as well as migration of iIba-1+ cells to the outside of the explant (P<0.05). This confirms the paracrine effect of the secretome in the spinal cord environment with a potential translatable effect in vivo. On this wise, we decided to combine the ASCs secretome with EES in a rat model of SCI (severe contusion) in vivo. We observed a synergetic effect of both treatments on the locomotor score (BBB scale), body weight support, maximum speed, number of steps and dragging time during the stepping cycle, with the combinatory approach demonstrating superior performance than control rats in all parameters analysed. We also detected an interesting result in the Randall Sellito test (pain response), which may suggest an increase in intraspinal plasticity after the treatment. Altogether, this provides evidence of the therapeutic potential of ASCs secretome after SCI, supported by indications on the positive effects exerted on neuroinflammation, axonal outgrowth and regeneration in vitro. This potential is also highlighted when combined with EES in vivo, with functional gains observed in the locomotor performance when compared to control.
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