The mutual interaction between the host spinal cord and grafted undifferentiated stem cells fosters the production of a lesion-induced secretome

摘要

Pathophysiology of spinal cord injury:Injury to the spinal cord results in loss of gray and white matter i.e.,it produces a segmental spinal cord lesion and,as a consequence leads to a fatal loss of motor,sensory and autonomic functions.Spinal cord injuries in humans and other mammals are not followed by the replacement of lost neurons and oligodendrocytes and regrowth of injured axons,instead they lead to permanent,fatal and incurable functional deficits.The primary physical injury is followed by a cascade of tissue-decaying events,called secondary injury,which leads to ischemia,vascular disruption,neuroinflammation,excitotoxicity,demyelination and death of neurons and glial cells(Silva et al.,2014;Figure 1A).The direct mechanical disruption of the vasculature results in the increased permeability of the blood-spinal cord barrier.Due to the leakiness of blood-spinal cord barrier and production of cytokines by activated microglia,a number of various immune cells(T lymphocytes,neutrophils and monocytes)invade the injury site.The macrophages generate a set of inflammatory cytokines such as tumor necrosis factor-α,interleukin(IL)-1α,IL-1β,and IL-6,which may further augment the secondary events(Ahuja et al.,2017).In addition,a number of other disruptive processes contribute to the heterogeneous and time-sensitive pathophysiology of spinal cord injury.