Exosomes Derived From CircAkap7-Modified Adipose-Derived Mesenchymal Stem Cells Protect Against Cerebral Ischemic Injury

Limin Xu; Haifeng Ji; Yufeng Jiang; Liying Cai; Xiaoyin Lai; Feifei Wu; Rongguo Hu; Xuelian Yang; Huan Bao; Mei Jiang

doi:10.3389/fcell.2020.569977

Exosomes Derived From CircAkap7-Modified Adipose-Derived Mesenchymal Stem Cells Protect Against Cerebral Ischemic Injury

Front Cell Dev Biol. 2020 Oct 2:8:569977. doi: 10.3389/fcell.2020.569977. eCollection 2020.

Authors

Limin Xu¹, Haifeng Ji², Yufeng Jiang³, Liying Cai², Xiaoyin Lai², Feifei Wu², Rongguo Hu², Xuelian Yang², Huan Bao⁴, Mei Jiang²

Affiliations

¹ Department of Clinical Laboratory, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, China.
² Department of Neurology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, China.
³ Department of Clinical Medicine, Clinic Medical College of Anhui Medical University, Hefei, China.
⁴ Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Abstract

Background: Cerebral ischemic injury is a complicated pathological process. Adipose-derived stromal cells (ADSCs) have been used as a therapeutic strategy, with their therapeutic effects chiefly attributed to paracrine action rather than trans-differentiation. Studies have shown that circAkap7 was found to be downregulated in a mouse model of transient middle cerebral artery occlusion (tMCAO).

Methods: To explore whether exosomes derived from circAkap7-modified ADSCs (exo-circAkap7) have therapeutic effects on cerebral ischemic injury, a mouse model of tMCAO, as well as an in vitro model of oxygen and glucose deprivation-reoxygenation (OGD-R) in primary astrocytes, were used.

Results: Results showed that treatment with exo-circAkap7 protected against tMCAO in mice, and in vitro experiments confirmed that co-culture with exo-circAkap7 attenuated OGD-R-induced cellular injury by absorbing miR-155-5p, promoting ATG12-mediated autophagy, and inhibiting NRF2-mediated oxidative stress.

Conclusion: We demonstrate here that exo-circAkap7 protected against cerebral ischemic injury by promoting autophagy and ameliorating oxidative stress.

Keywords: autophagy; cerebral ischemic injury; circular RNA; exosomes; oxidative stress.