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

Journal Article · Mon Oct 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.08.021· OSTI ID:23082576

Huang, Xiao ^[1]; Ding, Jing ^[2]; Li, Yufei ^[3]; Liu, Wenjuan; Ji, Jianlin ^[1]; Wang, Hao ^[4]; Wang, Xin ^[5]

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1. Department of Psychological Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)
2. Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China)
3. Department of Plastic Surgery, The NO. 455 Hospital of PLA, 338 West Huaihai Rd, Shanghai 200052 (China)
4. Teaching Center of Experimental Medicine, Shanghai Medical College, Fudan University, 138 Yixueyuan Rd, Shanghai 200032 (China)
5. The State Key Laboratory of Medical Neurobiology, the Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University and Department of Neurology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032 (China)

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 in exosome-mediated prevention of cerebral I/R injury by modulating apoptotic factors and promoting autophagy.

• OSTI ID: 23082576
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 371; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

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