Abstract
Adipose-derived stem cells (ADSCs) have been demonstrated to improve the microenvironment after a stroke. Increasing studies have confirmed that hypoxia pretreatment of ADSCs resulted in a better therapeutic effect, but the mechanism of treatment is unclear. We isolated ADSCs and exosomes. Then, constructed a middle cerebral artery occlusion (MCAO) mice model. High-throughput sequencing was used to identify the differential expression of circRNA. Immunofluorescence and ELISAs were used to detect the therapeutic effects of ADSC exosomes on MCAO. The luciferase reporter assay was used to detect the interaction relationships among circRNA-Ptpn4, miR-153-3p, and Nrf2. This study showed that exosomes from hypoxia pretreatment of ADSCs had significant effects in promoting functional recovery following in vivo MCAO, through suppressed inflammatory factor expression, and shifting the microglial from M1 to M2 polarization activation. The results showed that circRNA-Ptpn4 was highly expressed during hypoxia pretreatment of ADSCs exosomes. Exosomes from circ-Ptpn4-modified ADSCs had a greater ability to promote functional recovery. The circ-Ptpn4 delivered from ADSC exosomes induced microglia/macrophage polarization from M1 to M2 by suppressing miR-153-3p and enhancing Nrf2 expressions. Taken together, the results showed that exosomes from circRNA-Ptpn4 modified ADSC treatment repaired nerve damage caused by cerebral infarction by inducing microglial M1/M2 polarization.
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Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Change history
10 November 2023
A Correction to this paper has been published: https://doi.org/10.1007/s11010-023-04877-y
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The study was supported by research grants from The National Natural Science Foundation of China (Grant Nos. 82127807 and 82003142) and the Shanghai Key Laboratory of Molecular Imaging (18DZ2260400).
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MM J, YB C and G H contributed to the study conception and design. All authors collected the data and performed the data analysis. All authors contributed to the interpretation of the data and the completion of figures and tables. All authors contributed to the drafting of the article and final approval of the submitted version.
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Wang, F., Jiang, M., Chi, Y. et al. Exosomes from circRNA-Ptpn4 can modify ADSC treatment and repair nerve damage caused by cerebral infarction by shifting microglial M1/M2 polarization. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04824-x
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DOI: https://doi.org/10.1007/s11010-023-04824-x