Exosomal miR-125b-5p derived from adipose-derived mesenchymal stem cells enhance diabetic hindlimb ischemia repair via targeting alkaline ceramidase 2

Journal of Nanobiotechnology

Research

Hewei Xiong¹  Cheng Wang²  Guoyong Jiang²  Xuejiao Xiang²  Jiahe Guo²  Tao Jiang²  Chengcheng Li²  Xiaofan Yang²  Yu Kang²  Xiang Xu²  Jing Chen²  Zhenbing Chen²  Maojie Zhang²  Gui Wan²  Chengqi Yan²  Kaituo Xiang²  Wenqing Li³  Sen Ren⁴  Yue Sun⁵ 

[1] Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Department of Hand and Foot Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, 518052, Shenzhen, China;Department of Neurosurgery, Zhongnan Hospital of Wuhan University, 430071, Wuhan, China;The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, 430022, Wuhan, China;

关键词: Adipose-derived mesenchymal stem cells;    Exosomes;    miR-125b-5p;    Hindlimb ischemia;    Alkaline ceramidase 2;    Bioinformatics analysis;   

DOI  :  10.1186/s12951-023-01954-8

 received in 2023-04-06, accepted in 2023-06-03,  发布年份 2023

来源: Springer

【 摘 要 】

IntroductionIschemic diseases caused by diabetes continue to pose a major health challenge and effective treatments are in high demand. Mesenchymal stem cells (MSCs) derived exosomes have aroused broad attention as a cell-free treatment for ischemic diseases. However, the efficacy of exosomes from adipose-derived mesenchymal stem cells (ADSC-Exos) in treating diabetic lower limb ischemic injury remains unclear.MethodsExosomes were isolated from ADSCs culture supernatants by differential ultracentrifugation and their effect on C2C12 cells and HUVECs was assessed by EdU, Transwell, and in vitro tube formation assays separately. The recovery of limb function after ADSC-Exos treatment was evaluated by Laser-Doppler perfusion imaging, limb function score, and histological analysis. Subsequently, miRNA sequencing and rescue experiments were performed to figure out the responsible miRNA for the protective role of ADSC-Exos on diabetic hindlimb ischemic injury. Finally, the direct target of miRNA in C2C12 cells was confirmed by bioinformatic analysis and dual-luciferase report gene assay.ResultsADSC-Exos have the potential to promote proliferation and migration of C2C12 cells and to promote HUVECs angiogenesis. In vivo experiments have shown that ADSC-Exos can protect ischemic skeletal muscle, promote the repair of muscle injury, and accelerate vascular regeneration. Combined with bioinformatics analysis, miR-125b-5p may be a key molecule in this process. Transfer of miR-125b-5p into C2C12 cells was able to promote cell proliferation and migration by suppressing ACER2 overexpression.ConclusionThe findings revealed that miR-125b-5p derived from ADSC-Exos may play a critical role in ischemic muscle reparation by targeting ACER2. In conclusion, our study may provide new insights into the potential of ADSC-Exos as a treatment option for diabetic lower limb ischemia.

【 授权许可】

CC BY   
© The Author(s) 2023

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