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- Title
Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation.
- Authors
Rau, Cheng-Shyuan; Kuo, Pao-Jen; Wu, Shao-Chun; Huang, Lien-Hung; Lu, Tsu-Hsiang; Wu, Yi-Chan; Wu, Chia-Jung; Lin, Chia-Wei; Tsai, Chia-Wen; Hsieh, Ching-Hua
- Abstract
Exosomes secreted by adipose-derived stem cells (ADSC-exo) reportedly improve nerve regeneration after peripheral nerve injury. Herein, we investigated whether pretreatment of ADSCs with FK506, an immunosuppressive drug that enhances nerve regeneration, could secret exosomes (ADSC-F-exo) that further augment nerve regeneration. Designed exosomes were topically applied to injured nerve in a mouse model of sciatic nerve crush injury to assess the nerve regeneration efficacy. Outcomes were determined by histomorphometric analysis of semi-thin nerve sections stained with toluidine blue, mouse neurogenesis PCR array, and neurotrophin expression in distal nerve segments. Isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile potential exosomal proteins facilitating nerve regeneration. We observed that locally applied ADSC-exo and ADSC-F-exo significantly enhanced nerve regeneration after nerve crush injury. Pretreatment of ADSCs with FK506 failed to produce exosomes possessing more potent molecules for enhanced nerve regeneration. Proteomic analysis revealed that of 192 exosomal proteins detected in both ADSC-exo and ADSC-F-exo, histone deacetylases (HDACs), amyloid-beta A4 protein (APP), and integrin beta-1 (ITGB1) might be involved in enhancing nerve regeneration.
- Subjects
PERIPHERAL nerve injuries; TACROLIMUS; STEM cells; SCIATIC nerve injuries; EXOSOMES; NERVOUS system regeneration
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 16, p8545
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22168545