Enhanced Nerve Regeneration by Exosomes Secreted by Adipose-Derived Stem Cells with or without FK506 Stimulation

被引：26

作者：

Rau, Cheng-Shyuan ^{[1
,2
]}

Kuo, Pao-Jen ^{[2
,3
]}

Wu, Shao-Chun ^{[2
,4
]}

Huang, Lien-Hung ^{[1
,2
]}

Lu, Tsu-Hsiang ^{[2
,3
]}

Wu, Yi-Chan ^{[2
,3
]}

Wu, Chia-Jung ^{[2
,3
]}

Lin, Chia-Wei ^{[2
,3
]}

Tsai, Chia-Wen ^{[2
,3
]}

Hsieh, Ching-Hua ^{[2
,3
,5
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Dept Neurosurg, Kaohsiung 83301, Taiwan

[2] Chang Gung Univ, Coll Med, Kaohsiung 83301, Taiwan

[3] Kaohsiung Chang Gung Mem Hosp, Dept Plast & Reconstruct Surg, Kaohsiung 83301, Taiwan

[4] Kaohsiung Chang Gung Mem Hosp, Dept Anesthesiol, Kaohsiung 83301, Taiwan

[5] Chang Gung Mem Hosp, Ctr Vascularized Composite Allotransplantat, Taoyuan 33305, Taiwan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 16期

关键词：

sciatic nerve crush injury; peripheral nerve regeneration; exosome; adipose-derived stem cells (ADSC); tacrolimus (FK506); proteomic analysis; PERIPHERAL-NERVE; ERECTILE DYSFUNCTION; NEURITE OUTGROWTH; NEUROPATHIC PAIN; APOLIPOPROTEIN-E; INJURY; REMYELINATION; DEACETYLASES; TACROLIMUS; EXPRESSION;

D O I：

10.3390/ijms22168545

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：14

共 78 条

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