Exosomes derived from PEDF modified adipose-derived mesenchymal stem cells ameliorate cerebral ischemia-reperfusion injury by regulation of autophagy and apoptosis.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Increasing evidence suggest that exosomes from mesenchymal stem cells have therapeutic effects in cerebral ischemia-reperfusion (I/R) injury, but the underlying mechanisms are unclear. Pigment epithelium-derived factor (PEDF) is a multifunctional protein that exhibits anti-inflammatory, antioxidative, and neuroprotective properties. We investigated the involvement of PEDF in I/R, using adipose-derived mesenchymal stem cells (ADSCs) isolated from rat. PEDF-overexpressing ADSCs were constructed and exosomes from ADSCs were isolated. SY-5Y cells were employed to identify the protective effects of exosomes in oxygen-glucose deprivation (OGD) experiments. Exosome treatment suppressed OGD-induced apoptosis by inhibiting the two-step caspase dependent (caspase-9 and caspase-3) apoptotic pathway. Increasing the PEDF content of exosomes further promoted the protective effect against OGD-induced apoptosis by activating autophagy, while blocking autophagy reduced the effect of PEDF-containing exosomes. We constructed a middle cerebral artery occlusion-reperfusion (MCAO) model using male Sprague-Dawley rats to identify the role of PEDF in exosome-mediated neuroprotection. These in vivo experiments further confirmed that exosomes from PEDF-modified ADSCs ameliorated cerebral I/R injury by activating autophagy and suppressing neuronal apoptosis. These findings suggest that PEDF plays a role

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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