Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke

Background: Mesenchymal stem cells (MSCs) hold great potential as a therapy for stroke and have previously been shown to promote recovery in preclinical models of cerebral ischaemia. MSCs secrete a wide range of growth factors, chemokines, cytokines and extracellular vesicles-collectively termed the secretome. In this study, we assessed for the first time the efficacy of the IL-1 alpha-primed MSC-derived secretome on brain injury and functional recovery after cerebral ischaemia. Methods: Stroke was induced in male C57BL/6 mice using the intraluminal filament model of middle cerebral artery occlusion. Conditioned medium from IL-1 alpha-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection. Results: IL-1 alpha-primed MSC-derived conditioned medium treatment at the time of stroke led to a similar to 30% reduction in lesion volume at 48 h and was associated with modest improvements in body mass gain, 28-point neurological score and nest building. Administration of MSC-derived conditioned medium at 24 h post-stroke led to improved nest building and neurological score despite no observed differences in lesion volume at day 2 post-stroke. Conclusions: Our results show for the first time that the administration of conditioned medium from IL-1 alpha-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.