Mesenchymal stem cells and treadmill training enhance function and promote tissue preservation after spinal cord injury

Abstract

Spinal cord injury (SCI) is considered a serious neurological disorder that can lead to severe sensory, motor and autonomic deficits. In this work, we investigated whether cell therapy associated with physical activity after mouse SCI could promote morphological and functional outcomes, using a lesion model established by our group. Mesenchymal stem cells (8 × 10⁵ cells/2 µL) or DMEM (2 µL), were injected in the epicenter of the lesion at 7 days after SCI, and the mice started a moderate treadmill training 14 days after injury. Functional assessments were performed weekly up to 8 weeks after injury when the morphological analyses were also performed. Four injured groups were analyzed: DMEM (SCI plus DMEM injection), MSCT (SCI plus MSC injection), DMEM + TMT (SCI plus DMEM injection and treadmill training) and MSCT + TMT (SCI plus MSC injection and treadmill training). The animals that received the combined therapy (MSCT + TMT) were able to recover and maintained the better functional results throughout the analyzed period. The morphometric analysis from MSCT + TMT group evidenced a larger spared white matter area and a higher number of preserved myelinated fibers with the majority of them reaching the ideal G-ratio values, when compared to other groups. Ultrastructural analysis from this group, using transmission electron microscopy, showed better tissue preservation with few microcavitations and degenerating nerve fibers. Also, this group exhibited a significantly higher neurotrophin 4 (NT4) expression as compared to the other groups. The results provided by this study support the conclusion that the association of strategies is a potential therapeutic approach to treat SCI, with the possibility of translation into the clinical practice.

Keywords: Exercise; Functional recovery; Mesenchymal stem cell; Regeneration; Spinal cord injury; Treadmill training.