Abstract
Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion.
Highlights
Traumatic spinal cord injury is a complex clinical condition considered to be one of the most debilitating neurological disorders in industrialized societies
At 56 days post-injury, we examined the integrity of longitudinal fiber tracts using diffusion tensor imaging (DTI) in a 9 mm segment of the spinal cord centered on the lesion
To the best of our knowledge, this constitutes the first report showing that an intralesional application of EVs successfully improves long-term structural and functional outcomes in a rat model of Traumatic spinal cord injury (tSCI)
Summary
Traumatic spinal cord injury (tSCI) is a complex clinical condition considered to be one of the most debilitating neurological disorders in industrialized societies. The principal sources of pro-inflammatory cytokines at the lesion site are the microglia and the ‘‘classically-activated’’ macrophages (Pineau and Lacroix, 2007; Zhou et al, 2014; Honjoh et al, 2019) The former are the resident immune cells of the central nervous tissue, which upregulate the secretion of pro-inflammatory cytokines, such as interleukin-1α and β (IL-1α and IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), very rapidly after tSCI (Hayashi et al, 2000; Pan et al, 2002; Yang et al, 2004; Pineau and Lacroix, 2007). The scar is believed to impede or even block regenerative processes (Karimi-Abdolrezaee and Billakanti, 2012; Anderson et al, 2016; Bellver-Landete et al, 2019; Bradbury and Burnside, 2019)
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