EFFECTS OF EXTRACELLULAR VESICLES ISOLATED FROM SUBVENTRICULAR ZONE ON MOLECULAR CHANGES FOLLOWING SPINAL CORD INJURY ON WISTAR RATS
Abstract
Spinal cord injury (SCI) may occur as a result of traumatic crash to the spine that dislocates one or many vertebrae. SCI has two events to bring about the injury in the spinal cord that result at the end it will lead to bad consequences and loss of neurons; SCI complications are general loss of motor and sensory function. Extracellular vesicles (EVs) are very small vesicles produced by cells that contribute to cell to cell communication, transferring bioactive lipids, proteins, RNA. The aim of this research is to determine the effect of EVs on inflammasomes complex after SCI on rats. EVs were harvested characterized and cultured as exosomes, the animals are divided to 5 groups: control, sham, vehicle, SCI + treatment, SCI + EVs group. Spinal cord injury was induced using weight compression. 10 μl of EVs were injected intrathecally into lumber cistern in a space between L4-L5 laminae slowly. Gene expression of Caspase-1, ASC and NLRP3 were determined by RT-PCR. Western blot for determining the protein content of the inflammasomes were carried out. SCI up regulated the level of inflammasome complex both mRNA and proteins. Inthrathecal injection of EVs down regulated the inflammasome complex and make neuronal recovery. SCI can up regulate the level of inflammasome complex both mRNA and proteins. EVs are good therapeutic agent for SCI and increase neuronal recovery, inthrathecal injection is the best method of injection MSCs for treatment of SCI.
References
Agostinello, J., Battistuzzo, C. R., Skeers, P., Bernard, S. & Batchelor, P. E. 2017. Early Spinal Surgery Following Thoracolumbar Spinal Cord Injury: Process of Care From Trauma to Theater. Spine, 42: E617-E623.
Aligholi, H., Hassanzadeh, G., Azari, H., Rezayat, S. M., Mehr, S. E., Akbari, M., Attari, F., Khaksarian, M. & Gorji, A. 2014. A new and safe method for stereotactically harvesting neural stem/progenitor cells from the adult rat subventricular zone. Journal of neuroscience methods, 225: 81-89.
Allison, D. J., Thomas, A., Beaudry, K. & Ditor, D. S. 2016. Targeting inflammation as a treatment modality for neuropathic pain in spinal cord injury: a randomized clinical trial. Journal of neuroinflammation, 13: 152.
Anderson, D. J. 2001. Stem cells and pattern formation in the nervous system: the possible versus the actual. Neuron, 30: 19-35.
Azari, H., Rahman, M., Sharififar, S. & Reynolds, B. A. 2010. Isolation and expansion of the adult mouse neural stem cells using the neurosphere assay. JoVE (Journal of Visualized Experiments), 20(45): 2393.
Baglio, S. R., Pegtel, D. M. & Baldini, N. 2012. Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy. Frontiers in physiology, 3: 359.
Benito-Martin, A., Di Giannatale, A., Ceder, S. & Peinado, H. 2015. The new deal: a potential role for secreted vesicles in innate immunity and tumor progression. Frontiers in immunology, 6: 66.
Camussi, G., Deregibus, M. C. & Cantaluppi, V. 2013. Role of stem-cell-derived microvesicles in the paracrine action of stem cells. Organogenesis, 7(2): 105–115 Portland Press Limited.
De Rivero Vaccari, J. P., Lotocki, G., Marcillo, A. E., Dietrich, W. D. & Keane, R. W. 2008. A molecular platform in neurons regulates inflammation after spinal cord injury. Journal of Neuroscience, 28: 3404-3414.
Farahabadi, A., Akbari, M., Pishva, A. A., Zendedel, A., Arabkheradmand, A., Beyer, C., Dashti, N. & Hassanzadeh, G. 2016. Effect of Progesterone Therapy on TNF-α and iNOS Gene Expression in Spinal Cord Injury Model. Acta Medica Iranica, 54: 345-351.
Franchi, L., Muñoz-Planillo, R. & Núñez, G. 2012. Sensing and reacting to microbes through the inflammasomes. Nature immunology, 13: 325.
Haney, M. J., Klyachko, N. L., Zhao, Y., Gupta, R., Plotnikova, E. G., He, Z., Patel, T., Piroyan, A., Sokolsky, M. & Kabanov, A. V. 2015. Exosomes as drug delivery vehicles for Parkinson's disease therapy. Journal of Controlled Release, 207: 18-30.
Ijaz, S., Mohammed, I., Gholaminejhad, M., Mokhtari, T., Akbari, M. & Hassanzadeh, G. 2019. Modulating Pro-inflammatory Cytokines, Tissue Damage Magnitude, and Motor Deficit in Spinal Cord Injury with Subventricular Zone-Derived Extracellular Vesicles. Journal of Molecular Neuroscience, 70(3):458-466.
Katsuda, T., Kosaka, N., Takeshita, F. & Ochiya, T. 2013. The therapeutic potential of mesenchymal stem cellâ€derived extracellular vesicles. Proteomics, 13: 1637-1653.
Liang, F., Li, C., Gao, C., Li, Z., Yang, J., Liu, X. & Wang, Y. 2015. Effects of hyperbaric oxygen therapy on NACHT domain-leucine-rich-repeat-and pyrin domain-containing protein 3 inflammasome expression in rats following spinal cord injury. Molecular medicine reports, 11: 4650-4656.
Liu, W., Wang, Y., Gong, F., Rong, Y., Luo, Y., Tang, P., Zhou, Z., Zhou, Z., Xu, T. & Jiang, T. 2019. Exosomes derived from bone mesenchymal stem cells repair traumatic spinal cord injury by suppressing the activation of A1 neurotoxic reactive astrocytes. Journal of neurotrauma, 36:469-484.
Logozzi, M., Mizzoni, D., Bocca, B., Di Raimo, R., Petrucci, F., Caimi, S., Alimonti, A., Falchi, M., Cappello, F. & Campanella, C. 2019. Human primary macrophages scavenge AuNPs and eliminate it through exosomes. A natural shuttling for nanomaterials. European Journal of Pharmaceutics and Biopharmaceutics, 137: 23-36.
Lois, C. & Alvarez-Buylla, A. 1994. Long-distance neuronal migration in the adult mammalian brain. Science, 264: 1145-1149.
Lu, Y., Zhou, Y., Zhang, R., Wen, L., Wu, K., Li, Y., Yao, Y., Duan, R. & Jia, Y. 2019. Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Recovery Following Spinal Cord Injury via Improvement of the Integrity of the Blood-Spinal Cord Barrier. Frontiers in neuroscience, 12(13):209.
Marote, A., Teixeira, F. G., Mendes-Pinheiro, B. & Salgado, A. J. 2016. MSCs-derived exosomes: cell-secreted nanovesicles with regenerative potential. Frontiers in pharmacology, 7: 231.
Mause, S. F. & Weber, C. 2010. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circulation research, 107: 1047-1057.
Mcculloh, C. J., Olson, J. K., Wang, Y., Zhou, Y., Tengberg, N. H., Deshpande, S. & Besner, G. E. 2018. Treatment of experimental necrotizing enterocolitis with stem cell-derived exosomes. Journal of pediatric surgery, 53: 1215-1220.
Menn, B., Garcia-Verdugo, J. M., Yaschine, C., Gonzalez-Perez, O., Rowitch, D. & Alvarez-Buylla, A. 2006. Origin of oligodendrocytes in the subventricular zone of the adult brain. Journal of Neuroscience, 26: 7907-7918.
Mohamadi, Y., Moghahi, S. M. H. N., Mousavi, M., Borhani-Haghighi, M., Abolhassani, F., Kashani, I. R. & Hassanzadeh, G. 2019. Intrathecal transplantation of Wharton’s jelly mesenchymal stem cells suppresses the NLRP1 inflammasome in the rat model of spinal cord injury. Journal of chemical neuroanatomy, 97: 1-8.
Mohamadi, Y., Mousavi, M., Moogahi, S. M. H. N., Abolhassani, F., Ijaz, S. & Hassanzadeh, G. 2018. Effect of Wharton's Jelly Derived Mesenchymal Stem Cells on the Expression of NLRP3 Receptor and Neuroinflammation in Experimental Spinal Cord Injury. Journal of Clinical & Diagnostic Research, 12(10): 33-40.
Mohammed, I., Ijaz, S., Mokhtari, T., Gholaminejhad, M., Mahdavipour, M., Jameie, B., Akbari, M. & Hassanzadeh, G. 2020. Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation. Metabolic Brain Disease, 35: 809–818.
Mohankumar, S. & Patel, T. 2015. Extracellular vesicle long noncoding RNA as potential biomarkers of liver cancer. Briefings in functional genomics, 15: 249-256.
Morel, O., Toti, F., Hugel, B. & Freyssinet, J.-M. 2004. Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Current opinion in hematology, 11: 156-164.
Mousavi, M., Hedayatpour, A., Mortezaee, K., Mohamadi, Y., Abolhassani, F. & Hassanzadeh, G. 2019. Schwann cell transplantation exerts neuroprotective roles in rat model of spinal cord injury by combating inflammasome activation and improving motor recovery and remyelination. Metabolic Brain Disease, 34(4):1117-1130.
Nikmehr, B., Bazrafkan, M., Hassanzadeh, G., Shahverdi, A., Gilani, M. A. S., Kiani, S., Mokhtari, T. & Abolhassani, F. 2017. The correlation of gene expression of inflammasome indicators and impaired fertility in rat model of spinal cord injury: a time course study. Urology journal, 14: 5057-5063.
Nishida-Aoki, N. & Ochiya, T. 2015. Interactions between cancer cells and normal cells via miRNAs in extracellular vesicles. Cellular and Molecular Life Sciences, 72: 1849-1861.
Petrilli, V., Papin, S., Dostert, C., Mayor, A., Martinon, F. & Tschopp, J. 2007. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell death and differentiation, 14: 1583.
Rani, S., Ryan, A. E., Griffin, M. D. & Ritter, T. 2015. Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications. Molecular Therapy, 23: 812-823.
Rong, Y., Liu, W., Wang, J., Fan, J., Luo, Y., Li, L., Kong, F., Chen, J., Tang, P. & Cai, W. 2019. Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy. Cell death & disease, 10: 340.
Schorey, J. S. & Bhatnagar, S. 2008. Exosome function: from tumor immunology to pathogen biology. Traffic, 9: 871-881.
Schroder, K. & Tschopp, J. 2010. The inflammasomes. cell, 140: 821-832.
Sloka, J. & Stefanelli, M. 2005. The mechanism of action of methylprednisolone in the treatment of multiple sclerosis. Multiple Sclerosis Journal, 11: 425-432.
Thuret, S., Moon, L. D. & Gage, F. H. 2006. Therapeutic interventions after spinal cord injury. Nature Reviews Neuroscience, 7: 628-643.
Vogel, A., Upadhya, R. & Shetty, A. K. 2018. Neural stem cell derived extracellular vesicles: attributes and prospects for treating neurodegenerative disorders. EBioMedicine, 38:273-282
Xia, C., Cai, Y., Lin, Y., Guan, R., Xiao, G. & Yang, J. 2016. MiRâ€133bâ€5p regulates the expression of the heat shock protein 70 during rat neuronal cell apoptosis induced by the gp120 V3 loop peptide. Journal of medical virology, 88: 437-447.
Xin, H., Katakowski, M., Wang, F., Qian, J.-Y., Liu, X. S., Ali, M. M., Buller, B., Zhang, Z. G. & Chopp, M. 2017. MicroRNA-17–92 cluster in exosomes enhance neuroplasticity and functional recovery after stroke in rats. Stroke, 48: 747-753.
Yang, Y., Ye, Y., Su, X., He, J., Bai, W. & He, X. 2017. MSCs-derived exosomes and neuroinflammation, neurogenesis and therapy of traumatic brain injury. Frontiers in cellular neuroscience, 11: 55.
Zendedel, A., Johann, S., Mehrabi, S., Joghataei, M.-T., Hassanzadeh, G., Kipp, M. & Beyer, C. 2016. Activation and regulation of NLRP3 inflammasome by intrathecal application of SDF-1a in a spinal cord injury model. Molecular neurobiology, 53:3063-3075.
Zhang, Y., Kim, M. S., Jia, B., Yan, J., Zuniga-Hertz, J. P., Han, C. & Cai, D. 2017. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature, 548: 52.
Copyright (c) 2022 FUDMA JOURNAL OF SCIENCES
This work is licensed under a Creative Commons Attribution 4.0 International License.
FUDMA Journal of Sciences
