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Intravenous transplantation of olfactory ensheathing cells reduces neuroinflammation after spinal cord injury via interleukin-1 receptor antagonist.


ABSTRACT: Rationale: Olfactory ensheathing cell (OEC) transplantation has emerged as a promising therapy for spinal cord injury (SCI) repair. In the present study, we explored the possible mechanisms of OECs transplantation underlying neuroinflammation modulation. Methods: Spinal cord inflammation after intravenous OEC transplantation was detected in vivo and ex vivo by translocator protein PET tracer [18F]F-DPA. To track transplanted cells, OECs were transduced with enhanced green fluorescent protein (eGFP) and HSV1-39tk using lentiviral vector and were monitored by fluorescence imaging and [18F]FHBG study. Protein microarray analysis and ELISA studies were employed to analyze differential proteins in the injured spinal cord after OEC transplantation. The anti-inflammation function of the upregulated protein was also proved by in vitro gene knocking down experiments and OECs/microglia co-culture experiment. Results: The inflammation in the spinal cord was decreased after OEC intravenous transplantation. The HSV1-39tk-eGFP-transduced OECs showed no accumulation in major organs and were found at the injury site. After OEC transplantation, in the spinal cord tissues, the interleukin-1 receptor antagonist (IL-1Ra) was highly upregulated while many chemokines, including pro-inflammatory chemokines IL-1?, IL-1? were downregulated. In vitro studies confirmed that lipopolysaccharide (LPS) stimulus triggered OECs to secrete IL-1Ra. OECs significantly suppressed LPS-stimulated microglial activity, whereas IL-1Ra gene knockdown significantly reduced their ability to modulate microglial activity. Conclusion: The OECs that reached the lesion site were activated by the release of pro-inflammatory cytokines from activated microglia in the lesion site and secreted IL-1Ra to reduce neuroinflammation. Intravenous transplantation of OECs has high therapeutic effectiveness for the treatment of SCI via the secretion of IL-1Ra to reduce neuroinflammation.

SUBMITTER: Zhang L 

PROVIDER: S-EPMC7738890 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Intravenous transplantation of olfactory ensheathing cells reduces neuroinflammation after spinal cord injury <i>via</i> interleukin-1 receptor antagonist.

Zhang Lijian L   Zhuang Xiaoqing X   Kotitalo Päivi P   Keller Thomas T   Krzyczmonik Anna A   Haaparanta-Solin Merja M   Solin Olof O   Forsback Sarita S   Grönroos Tove J TJ   Han Chunlei C   López-Picón Francisco R FR   Xia Hechun H  

Theranostics 20210101 3


<b>Rationale:</b> Olfactory ensheathing cell (OEC) transplantation has emerged as a promising therapy for spinal cord injury (SCI) repair. In the present study, we explored the possible mechanisms of OECs transplantation underlying neuroinflammation modulation. <b>Methods:</b> Spinal cord inflammation after intravenous OEC transplantation was detected <i>in vivo</i> and <i>ex vivo</i> by translocator protein PET tracer [<sup>18</sup>F]F-DPA. To track transplanted cells, OECs were transduced with  ...[more]

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