Immune effector mechanisms play key roles in the progressive（secondary）neurodegenerative changes that follow spinal cord injury（SCI）.In our recent paper（Brennan et al.,2015）,we showed that the inflammatory respo...Immune effector mechanisms play key roles in the progressive（secondary）neurodegenerative changes that follow spinal cord injury（SCI）.In our recent paper（Brennan et al.,2015）,we showed that the inflammatory response to SCI includes rapid and robust activation of the innate immune complement system, with tissue levels of complement component 5a （C5a - an activation product generated by the proteolysis of complement factor 5 （C5）） peaking 12 to 24 hours post-iniurv.展开更多
Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal rege...Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury,as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier.To develop an effective non-invasive treatment strategy for SCI in clinic,we generated an autologous plasma exosome(AP-EXO)based biological scaffold where AP-EXO was loaded with neuron targeting peptide(RVG)and growth-facilitating peptides(ILP and ISP).This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment,thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice.More importantly,in ex vivo,human plasma exosomes(HP-EXO)loaded with combinatory peptides of RVG,ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice.Combining the efficacy and safety,the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI.It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.展开更多
基金supported by Spinal Cure Australia(Career Development Fellowship to MJR),The University of Queensland,and the National Health and Medical Research Council of Australia(Project Grant 1060538 to MJR)
文摘Immune effector mechanisms play key roles in the progressive（secondary）neurodegenerative changes that follow spinal cord injury（SCI）.In our recent paper（Brennan et al.,2015）,we showed that the inflammatory response to SCI includes rapid and robust activation of the innate immune complement system, with tissue levels of complement component 5a （C5a - an activation product generated by the proteolysis of complement factor 5 （C5）） peaking 12 to 24 hours post-iniurv.
基金This work was supported by the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100),ChinaNational Natural Science Foundation of China(81930070)+3 种基金National Natural Science Foundation of China(82102560)the Natural Science Foundation of Shandong Province,China(ZR2021QH097)the No.69 General Fund of China Postdoctoral Science Foundation(2021M691936)Talent project of Shandong University(22480082063100),China.
文摘Spinal cord injury(SCI)causes motor,sensory and automatic impairment due to rarely axon regeneration.Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury,as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier.To develop an effective non-invasive treatment strategy for SCI in clinic,we generated an autologous plasma exosome(AP-EXO)based biological scaffold where AP-EXO was loaded with neuron targeting peptide(RVG)and growth-facilitating peptides(ILP and ISP).This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment,thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice.More importantly,in ex vivo,human plasma exosomes(HP-EXO)loaded with combinatory peptides of RVG,ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice.Combining the efficacy and safety,the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI.It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.
