scholarly journals Exosomes Secreted by Adipose-Derived Stem Cells Following FK506 Stimulation Reduce Autophagy of Macrophages in Spine after Nerve Crush Injury

2021 ◽  
Vol 22 (17) ◽  
pp. 9628
Author(s):  
Pao-Jen Kuo ◽  
Cheng-Shyuan Rau ◽  
Shao-Chun Wu ◽  
Chia-Wei Lin ◽  
Lien-Hung Huang ◽  
...  

Macrophages emerge in the milieu around innervated neurons after nerve injuries. Following nerve injury, autophagy is induced in macrophages and affects the regulation of inflammatory responses. It is closely linked to neuroinflammation, while the immunosuppressive drug tacrolimus (FK506) enhances nerve regeneration following nerve crush injury and nerve allotransplantation with additional neuroprotective and neurotrophic functions. The combined use of FK506 and adipose-derived stem cells (ADSCs) was employed in cell therapy for organ transplantation and vascularized composite allotransplantation. This study aimed to investigate the topical application of exosomes secreted by ADSCs following FK506 treatment (ADSC-F-exo) to the injured nerve in a mouse model of sciatic nerve crush injury. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ) were used to profile the potential exosomal proteins involved in autophagy. Immunohistochemical analysis revealed that nerve crush injuries significantly induced autophagy in the dorsal root ganglia and dorsal horn of the spinal segments. Locally applied ADSC-F-exo significantly reduced autophagy of macrophages in the spinal segments after nerve crush injury. Proteomic analysis showed that of the 22 abundant exosomal proteins detected in ADSC-F-exo, heat shock protein family A member 8 (HSPA8) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) are involved in exosome-mediated autophagy reduction.

2021 ◽  
Vol 22 (16) ◽  
pp. 8545
Author(s):  
Cheng-Shyuan Rau ◽  
Pao-Jen Kuo ◽  
Shao-Chun Wu ◽  
Lien-Hung Huang ◽  
Tsu-Hsiang Lu ◽  
...  

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.


2018 ◽  
Vol 58 (4) ◽  
pp. 566-572 ◽  
Author(s):  
Mathias Tremp ◽  
Lima Sprenger ◽  
Lucas Degrugillier ◽  
Dirk Johannes Schaefer ◽  
Srinivas Madduri ◽  
...  

2007 ◽  
Vol 205 (3) ◽  
pp. S92
Author(s):  
Terence M. Myckatyn ◽  
Christina Kenney ◽  
Alice Tong ◽  
Jessica Duan ◽  
Daniel Hunter ◽  
...  

1998 ◽  
Vol 96 (3-4) ◽  
pp. 245-254 ◽  
Author(s):  
Khalaf Al Moutaery ◽  
Mohammed Arshaduddin ◽  
Mohammad Tariq ◽  
Saleh Al Deeb

2018 ◽  
Vol 28 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Diego Noé Rodríguez Sánchez ◽  
Luiz Antonio de Lima Resende ◽  
Giovana Boff Araujo Pinto ◽  
Ana Lívia de Carvalho Bovolato ◽  
Fábio Sossai Possebon ◽  
...  

Crush injuries in peripheral nerves are frequent and induce long-term disability with motor and sensory deficits. Due to axonal and myelin sheath disruptions, strategies for optimized axonal regeneration are needed. Multipotent mesenchymal stromal cells (MSC) are promising because of their anti-inflammatory properties and secretion of neurotrophins. The present study investigated the effect of canine adipose tissue MSC (Ad-MSC) transplantation in an experimental sciatic nerve crush injury. Wistar rats were divided into three groups: sham ( n = 8); Crush+PBS ( n = 8); Crush+MSC ( n = 8). Measurements of sciatic nerve functional index (SFI), muscle mass, and electromyography (EMG) were performed. Canine Ad-MSC showed mesodermal characteristics (CD34-, CD45-, CD44+, CD90+ and CD105+) and multipotentiality due to chondrogenic, adipogenic, and osteogenic differentiation. SFI during weeks 3 and 4 was significantly higher in the Crush+MSC group ( p < 0.001). During week 4, the EMG latency in the Crush+MSC groups had better near normality ( p < 0.05). The EMG amplitude showed results close to normality during week 4 in the Crush+MSC group ( p < 0.04). There were no statistical differences in muscle weight between the groups ( p > 0.05), but there was a tendency toward weight gain in the Crush+MSC groups. Better motor functional recovery after crush and perineural canine Ad-MSC transplantation was observed during week 2. This was maintained till week 4. In conclusion, the canine Ad-MSC transplantation showed early pro-regenerative effects between 2–4 weeks in the rat model of sciatic nerve crush injury.


2017 ◽  
Vol 68 (5) ◽  
pp. 579-587 ◽  
Author(s):  
Majid Salehi ◽  
Mahdi Naseri-Nosar ◽  
Somayeh Ebrahimi-Barough ◽  
Mohammdreza Nourani ◽  
Ahmad Vaez ◽  
...  

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