Abstract
Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue.
Highlights
Treatment of spinal cord injury (SCI) faces several problems
Our work confirms that mesenchymal stem cells (MSCs) treatment is beneficial after SCI and is in accordance with previous studies reviewed by [4]
We show by two complementary locomotor tests that MSCs have the ability to significantly improve functional recovery
Summary
Treatment of spinal cord injury (SCI) faces several problems. First of all, the mechanical damage and axonal disruption in the spinal cord are followed by a progressive cascade of secondary deleterious reactions spreading to the adjacent spared tissue leading to lesion extension and worsening the situation [1]. These studies focused on neuroprotection or axonal regeneration, by modifying the injured environment to be beneficial for repair, by replacing lost cells, stimulating and guiding axonal growth or boosting remyelination [3,4,5,6] To act on these events, scientists often exploited the potential of cell therapy using transplantation of various cell types like Schwann cells [7,8], olfactory ensheathing cells [9,10], neural stem cells [11,12], bone marrow stromal cells [13,14], fibroblasts [15,16] and macrophages [17]. It appears that bone marrow stromal cells, called mesenchymal stem cells (MSCs) could take an interesting part in these strategies
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