Abstract
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-1α-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-1α-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection.
Results
IL-1α-primed MSC-derived conditioned medium treatment at the time of stroke led to a ~ 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-1α-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.
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-1α-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-1α-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection.
Results
IL-1α-primed MSC-derived conditioned medium treatment at the time of stroke led to a ~ 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-1α-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.
| Original language | English |
|---|---|
| Article number | 32 |
| Journal | Stem cell research & therapy |
| Volume | 11 |
| DOIs | |
| Publication status | Published - 21 Jan 2020 |
Bibliographical note
This work was supported by the Engineering and Physical Sciences Research Council (EPSRC, UK) and Medical Research Council (MRC, UK) Centre for Doctoral Training in Regenerative Medicine studentship grant EP/L014904/1 and the Stroke Association (TSA 2017/03).Keywords
- cell therapy
- conditioned medium
- mesenchymal stem cell
- secretome
- stroke
- Mesenchymal stem cell
- Stroke
- Cell therapy
- Conditioned medium
- Secretome
- FUNCTIONAL RECOVERY
- BEHAVIOR
- MODEL
- NEUROPROTECTION
- TRANSPLANTATION
- INFLAMMATION
- THERAPEUTIC BENEFIT
- CEREBRAL-ISCHEMIA
- BRAIN
- MARROW STROMAL CELLS