PMID- 36969321 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230328 IS - 2405-5808 (Electronic) IS - 2405-5808 (Linking) VI - 34 DP - 2023 Jul TI - Hypoxia-treated umbilical mesenchymal stem cell alleviates spinal cord ischemia-reperfusion injury in SCI by circular RNA circOXNAD1/ miR-29a-3p/ FOXO3a axis. PG - 101458 LID - 10.1016/j.bbrep.2023.101458 [doi] LID - 101458 AB - Spinal cord ischemia reperfusion (SCIR) injury leads to spinal cord function injury, neural dysfunction and sometimes paralysis or even paraplegia, which severely impair the physical and mental health of individuals. Mesenchymal stem cells (MSCs) are a group of stem cells that have been widely studied for treatment of various diseases. This work aimed to study the therapeutic potential of hypoxia-induced exosomal circular RNA OXNAD1 from human umbilical cord mesenchymal stem cells (HucMSCs) against SCIR. We established an in vivo rat spinal cord injury (SCI) model and conducted treatment with exosomes that isolated from hypoxia-HucMSCs. Hypoxia-HucMSCs-derived exosomal circOXNAD1 alleviated the spinal cord tissue injury in SCI, improved limb motor function, decreased production of inflammatory factors including the IL-1 beta, IL-6, and TNF-alpha. The in vitro hypoxia and reoxygenation (H/R) model demonstrated that Hypoxia-HucMSCs-derived exosomal circOXNAD1 improved neuron proliferation and alleviated apoptosis. Mechanistically, circOXNAD1 directly interact with miR-29a-3p and miR-29a-3p targets the 3'UTR of FOXO3a in neurons. Inhibition of miR-29a-3p and overexpression of FOXO3a reversed the effects of circOXNAD1 depletion in PC12 cell phenotypes. In conclusion, Hypoxia elevated the level circOXNAD1 in exosomes that derived from HuMSCs. The exosomal circOXNAD1 alleviated SCI through sponging miR-29a-3p and consequently elevated the FOXO3a expression. Our findings provided novel evidence for MSC-derived exosomal circOXNAD1in the treatment of SCI. CI - (c) 2023 Everunion Biotechnology Co., LTD. Tianjin. FAU - Wang, Xiujuan AU - Wang X AD - Technology Department, Everunion Biotechnology Co. LTD., Tianjin, China. FAU - Li, Wei AU - Li W AD - Technology Department, Everunion Biotechnology Co. LTD., Tianjin, China. FAU - Hao, MingYuan AU - Hao M AD - Technology Department, Everunion Biotechnology Co. LTD., Tianjin, China. FAU - Yang, Ying AU - Yang Y AD - Technology Department, Everunion Biotechnology Co. LTD., Tianjin, China. FAU - Xu, YongSheng AU - Xu Y AD - Technology Department, Everunion Biotechnology Co. LTD., Tianjin, China. LA - eng PT - Journal Article DEP - 20230320 PL - Netherlands TA - Biochem Biophys Rep JT - Biochemistry and biophysics reports JID - 101660999 PMC - PMC10033311 OTO - NOTNLM OT - Exosomes OT - FOXO3 OT - Ischemia-reperfusion injury OT - Mesenchymal stem cell OT - Spinal cord injury OT - circOXNAD1 OT - miR-29a-3p COIS- There are no conflicts of interest. EDAT- 2023/03/28 06:00 MHDA- 2023/03/28 06:01 PMCR- 2023/03/20 CRDT- 2023/03/27 03:36 PHST- 2022/11/30 00:00 [received] PHST- 2023/02/28 00:00 [revised] PHST- 2023/03/13 00:00 [accepted] PHST- 2023/03/27 03:36 [entrez] PHST- 2023/03/28 06:00 [pubmed] PHST- 2023/03/28 06:01 [medline] PHST- 2023/03/20 00:00 [pmc-release] AID - S2405-5808(23)00039-0 [pii] AID - 101458 [pii] AID - 10.1016/j.bbrep.2023.101458 [doi] PST - epublish SO - Biochem Biophys Rep. 2023 Mar 20;34:101458. doi: 10.1016/j.bbrep.2023.101458. eCollection 2023 Jul.