Bone targeting miR-26a loaded exosome-mimetics for bone regeneration therapy by activating Wnt signaling pathway

Hao, Liuzhi1,2; Huang, Shuwen1,3; Huang, Tongling1; Yi, Dan4; Wang, Chenmin5; Cheng, Lixin6; Guan, Min1; Wu, Jun5,7; Chen, Di4; Pan, Haobo1; Lu, William W.1,5; Zhao, Xiaoli1,2

2023-09-01

10.1016/j.cej.2023.144594

CHEMICAL ENGINEERING JOURNAL   Impact Factor & Quartile

1385-8947

1873-3212

Mesenchymal stem cell-derived exosomes (MSC-Exos) have shown great potential in the areas of bone regen-eration and treatment of age-related diseases. Engineered exosomes can integrate multiple functional compo-nents to achieve optimal, targeted therapeutic effects. This study combined large-scale generation, bone-targeting modification, and miR-26a loading for exosome-mimetics (EMs) to construct a cell-free delivery sys-tem that promotes bone regeneration with good biocompatibility. EMs were fabricated through sequential extrusion of MSCs and reached a 15-fold production yield compared to conventional exosome secretion. Systemic injection of Asp8-EM/miR-26a in mouse models accelerated bone-defect healing and prevented osteoporosis. The underlying mechanism involves miR-26a targeting glycogen synthase kinase-38 (GSK-38) to induce 8-catenin accumulation, thus activating Wnt signaling pathway and promoting bone regeneration. This study provides a feasible and effective strategy for modifying EMs to enhance bone regeneration.

MSCs Exosomes miR-26a Osteoporosis Bone targeting Bone regeneration

SCI

English

Others

National Natural Science Foundation of China[81972071] ; Guangdong Basic and Applied Basic Research Foundation[2021A1515010191] ; Science and Technology Research Funding of Shenzhen["JCYJ20210324102001003","JCYJ2020 0109150420892"] ; National Natural Science Foundation of China/Research Grants Council Joint Research Scheme[N_HKU753/21] ; Shenzhen Key Laboratory of Marine Biomaterials[ZDSY20 130401165820356]

Engineering

Engineering, Environmental ; Engineering, Chemical

WOS:001042541800001

ELSEVIER SCIENCE SA

ENGINEERING

Web of Science

1.Chinese Acad Sci, Inst Biomed & Biotechnol, Shenzhen Inst Adv Technol, Res Ctr Human Tissue & Organs Degenerat, Shenzhen 518055, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Jinan Univ, Guangdong Hong Kong Macau Inst CNS Regenerat, Key Lab CNS Regenerat, Minist Educ, Guangzhou 510632, Peoples R China
4.Chinese Acad Sci, Inst Biomed & Biotechnol, Shenzhen Inst Adv Technol, Res Ctr Comp Aided Drug Discovery, Shenzhen 518055, Peoples R China
5.Univ Hong Kong, Dept Orthopaed & Traumatol, Hong Kong 999077, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen 518020, Peoples R China
7.Univ Hong Kong, Shenzhen Hosp, Shenzhen Key Lab Innovat Technol Orthopaed Trauma, Shenzhen 518053, Peoples R China

Hao, Liuzhi,Huang, Shuwen,Huang, Tongling,et al. Bone targeting miR-26a loaded exosome-mimetics for bone regeneration therapy by activating Wnt signaling pathway[J]. CHEMICAL ENGINEERING JOURNAL,2023,471.

Hao, Liuzhi.,Huang, Shuwen.,Huang, Tongling.,Yi, Dan.,Wang, Chenmin.,...&Zhao, Xiaoli.(2023).Bone targeting miR-26a loaded exosome-mimetics for bone regeneration therapy by activating Wnt signaling pathway.CHEMICAL ENGINEERING JOURNAL,471.

Hao, Liuzhi,et al."Bone targeting miR-26a loaded exosome-mimetics for bone regeneration therapy by activating Wnt signaling pathway".CHEMICAL ENGINEERING JOURNAL 471(2023).