Exosome Therapy in Spinal Cord Injury: A Review

Shahrokh Khoshsirat, Aliasghar Keramatinia, Maryam Sadat Khoramgah, Saeed Vafaei-Nezhad, Somayeh Niknazar, Shahram Darabi, Foozhan Tahmasebinia, Hassan Peyvandi, Hojjat-Allah Abbaszadeh

Abstract


45

Background: Injuries to the spinal cord (SCI) are one of the most detrimental central nervous system (CNS) injuries in developing countries. Today, treatment is one of the major issues facing the medical profession, and to date, there is no known promising treatment capable of fully healing injuries. There are various methods to repair and improve SCI, including the use of stem cells particularly mesenchymal stem cells (MSCs). Various studies have been performed on applying these cells in the treatment of SCI, whose results have confirmed the efficacy of using these cells specifically due to the paracrine secretion of these cells including growth factors, chemokines, cytokines, and small extracellular vesicles. Interestingly, among these paracrine molecules, exosomes may have the maximum therapeutic value and as such is widely investigated by researchers.

Aim: to fully focus on the usage of stem cell-derived extracellular vesicles on the healing of SCI in animal models.

Conclusion: Taken together, the extracellular nanovesicles have promising therapeutic potentials and their use in the treatment of SCI has been rapidly growing. In this review, we elucidated the effect of exosomes derived from bone marrow MSCs in SCI.


Keywords


Exosome; Spinal Cord Injury; Mesenchymal stem cells

Full Text:

PDF

13

References


Massetti J, Stein DM, Spinal cord injury, in Neurocritical Care for the Advanced Practice Clinician. 2018 (pp. 269-288). Springer, Cham.

Jazayeri SB, Ataeepour M, Rabiee H, Motevalian SA, Saadat S, Vaccaro AR, Rahimi-Movaghar V. Prevalence of spinal cord injury in Iran: a 3-source capture-recapture study. Neuroepidemiology. 2015;45(1):28-33.

Kong F-L, Wang X-P, Li Y-N, and Wang H-X. The role of exosomes derived from cerebrospinal fluid of spinal cord injury in neuron proliferation in vitro. Artificial cells, nanomedicine, and biotechnology. 2018;46:200-5.

Angeli C, Ochsner J, and Harkema S. Effects of chronic baclofen use on active movement in an individual with a spinal cord injury. Spinal cord. 2012;50:925.

Chen S-w and Xie Y-f. Glial implications in transplantation therapy of spinal cord injury. Chinese Journal of Traumatology (English Edition). 2009;12:55-61.

Karimfar M H, Noorozian M, Mastery Farahani R, Sadat Khoramgah M, Azimi H, Keramatinia A A, et al . Stable Transfection of pEGFP-N1-MOG Plasmid to Utilize in Multiple Sclerosis Gene Therapy. ASJ. 2015;12(1):3-8.

Ahuja CS, Wilson JR, Nori S, Kotter MR, Druschel C, Curt A, Fehlings MG. Traumatic spinal cord injury. Nature Reviews Disease Primers. 2017;3:17018.

Anwar MA, Al Shehabi TS, Eid AH. Inflammogenesis of secondary spinal cord injury. Frontiers in cellular neuroscience. 2016;10:98.

Fu S, Lv R, Wang L, Hou H, Liu H, and Shao S. Resveratrol, an antioxidant, protects spinal cord injury in rats by suppressing MAPK pathway. Saudi journal of biological sciences. 2018 Feb 1;25(2):259-66.

Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2012;1822:675-84.

Peyvandi AA, Roozbahany NA, Peyvandi H, Abbaszadeh HA, Majdinasab N, Faridan M, Niknazar S. Critical role of SDF-1/CXCR4 signaling pathway in stem cell homing in the deafened rat cochlea after acoustic trauma. Neural regeneration research. 2018 Jan;13(1):154.

Tahmasebinia F, Pourgholaminejad A. The role of Th17 cells in auto-inflammatory neurological disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2017 Oct 3;79:408-16.

David S, Kroner A, Inflammation and Secondary Damage after Spinal Cord Injury, in Neural Regeneration. 2015, Elsevier. p. 245-61.

Pourgholaminejad A, Tahmasebinia F. The Role of Th17 Cells in Immunopathogenesis of Neuroinflammatory Disorders. InNeuroimmune Diseases 2019 (pp. 83-107). Springer, Cham.

Ahuja CS, Nori S, Tetreault L, Wilson J, Kwon B, Harrop J, Choi D, Fehlings MG. Traumatic spinal cord injury—repair and regeneration. Neurosurgery. 2017;80: S9-S22.

Fan B, Wei Z, Yao X, Shi G, Cheng X, Zhou X, Zhou H, Ning G, Kong X, Feng S. Microenvironment Imbalance of Spinal Cord Injury. Cell transplantation. 2018 Jun;27(6):853-66.

Raspa A, Pugliese R, Maleki M, Gelain F. Recent therapeutic approaches for spinal cord injury. Biotechnology and bioengineering. 2016;113:253-9.

Blesch A, Lu P, and Tuszynski MH. Neurotrophic factors, gene therapy, and neural stem cells for spinal cord repair. Brain research bulletin. 2002;57:833-8.

Assinck P, Duncan GJ, Hilton BJ, Plemel JR, Tetzlaff W. Cell transplantation therapy for spinal cord injury. Nature neuroscience. 2017;20:637.

Maldonado-Lasunción I, Verhaagen J, Oudega M. Mesenchymal Stem Cell-Macrophage Choreography Supporting Spinal Cord Repair. Neurotherapeutics. 2018 Jul 1;15(3):578-87.

Takahashi A, Nakajima H, Uchida K, Takeura N, Honjoh K, Watanabe S, Kitade M, Kokubo Y, Johnson WE, Matsumine A. Comparison of Mesenchymal Stromal Cells Isolated from Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury. Cell transplantation. 2018;27:1126-39.

Ruppert KA, Nguyen TT, Prabhakara KS, Furman NET, Srivastava AK, Harting MT, Cox CS, Olson SD. Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Modify Microglial Response and Improve Clinical Outcomes in Experimental Spinal Cord Injury. Scientific reports. 2018;8:480.

Huang JH, Yin XM, Xu Y, Xu CC, Lin X, Ye FB, Cao Y, Lin FY. Systemic administration of exosomes released from mesenchymal stromal cells attenuates apoptosis, inflammation, and promotes angiogenesis after spinal cord injury in rats. Journal of neurotrauma.2017 Dec 15;34(24):3388-96.

Lai RC, Yeo RWY, Lim SK. Mesenchymal stem cell exosomes. in Seminars in Cell & Developmental Biology. 2015 Apr 1 (Vol. 40, pp. 82-88). Academic Press.

Lankford KL, Arroyo EJ, Nazimek K, Bryniarski K, Askenase PW, Kocsis JD. Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord. PloS one. 2018 Jan 2;13(1):e0190358.

Marques SA, Almeida FM, Fernandes AM, dos Santos Souza C, Cadilhe DV, Rehen SK, and Martinez AMB. Predifferentiated embryonic stem cells promote functional recovery after spinal cord compressive injury. Brain research. 2010Aug 19;1349:115-28.

Abbaszadeh HA, Tiraihi T, Noori-Zadeh A, Delshad AR, Sadeghizade M, Taheri T. Human ciliary neurotrophic factor–overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury. Cytotherapy. 2015 Jul 1;17(7):912-21.

Khoshsirat S, Abbaszadeh HA, Ahrabi B, Bahrami M, Abdollahi MA, Khoramgah MS, Roozbahany NA, Darabi S. Evaluation of the effect of BMSCs condition media and methylprednisolone in TGF-β expression and functional recovery after an acute spinal cord injury. Bratislavske lekarske listy. 2018;119(11):684-91.

Karimfar MH, Peyvandi A, Noorozian M, Ahmadi Roozbahani N, Mastery Farahani R, Khoramgah MS, Azimi H, Bahadori Monfared A, Abbaszadeh HA. Repressing of SOX6 and SOX9 in situ chondrogenic differentiation of rat bone marrow stromal cells. Anatomical Sciences Journal. 2015 May 15;12(2):75-82.

Biancone L, Bruno S, Deregibus MC, Tetta C, Camussi G. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrology Dialysis Transplantation. 2012;27: 3037-42.

Lai RC, Arslan F, Lee MM, Sze NSK, Choo A, Chen TS, Salto-Tellez M, Timmers L, Lee CN, El Oakley RM. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem cell research. 2010;4:214-22.

Kingham PJ, Kolar MK, Novikova LN, Novikov LN, Wiberg M. Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair. Stem cells and development. 2013;23:741-54.

Tan SS, Yin Y, Lee T, Lai RC, Yeo RW, Zhang B, Choo A, Lim SK. Therapeutic MSC exosomes are derived from lipid raft microdomains in the plasma membrane. Journal of extracellular vesicles. 2013 Jan 1;2(1):22614.

Rufino-Ramos D, Albuquerque PR, Carmona V, Perfeito R, Nobre RJ de Almeida LP. Extracellular vesicles: novel promising delivery systems for therapy of brain diseases. Journal of Controlled Release. 2017;262: 247-58.

Colombo M, Raposo G, and Théry C. Biogenesis, secretion, intercellular interactions of exosomes and other extracellular vesicles. Annual review of cell and developmental biology. 2014;30:255-89.

Abbaszadeh H, Niknazar S, Darabi S, Ahmady Roozbahany N. Stem Cell Transplantation and Functional Recovery after Spinal Cord Injury: A Systematic Review and Meta-Analysis. Anatomy Cell Biol. 2018;51(3):180-8.

Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Molecular Therapy. 2011;19:1769-79.

Lai RC, Yeo RWY, Tan KH, Lim SK. Exosomes for drug delivery—a novel application for the mesenchymal stem cell. Biotechnology advances. 2013;31:543-51.

Lachenal G, Pernet-Gallay K, Chivet M, Hemming FJ, Belly A, Bodon G, Blot B, Haase G, Goldberg Y, and Sadoul R. Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Molecular and Cellular Neuroscience. 2011;46: 409-18.

Fauré J, Lachenal G, Hirrlinger J, Chatellard-Causse C, Blot B, Grange J, Schoehn G, Goldberg Y, Boyer V, Kirchhoff F. Exosomes are released by cultured cortical neurones. Molecular and Cellular Neuroscience. 2006;31:642-8.

de Rivero Vaccari JP, Brand III F, Adamczak S, Lee SW, Perez‐Barcena J, Wang MY, Bullock MR, Dietrich WD, Keane RW. Exosome‐mediated inflammasome signaling after central nervous system injury. Journal of neurochemistry. 2016;136:39-48.

Saadati F, Mahdikia H, Abbaszadeh HA, Abdollahifar MA, Khoramgah MS, Shokri B. Comparison of Direct and Indirect cold atmospheric-pressure plasma methods in the B 16 F 10 melanoma cancer cells treatment. Scientific reports. 2018 May 16;8(1):7689.

Krämer‐Albers EM, Bretz N, Tenzer S, Winterstein C, Möbius W, Berger H, Nave KA, Schild H, Trotter J. Oligodendrocytes secrete exosomes containing major myelin and stress‐protective proteins: Trophic support for axons? PROTEOMICS–Clinical Applications. 2007;1:1446-61.

Zhang Y, Chopp M, Meng Y, Katakowski M, Xin H, Mahmood A, Xiong Y. Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury. Journal of neurosurgery. 2015 Apr 1;122(4):856-67.

Sun G, Li G, Li D, Huang W, Zhang R, Zhang H, Duan Y, Wang B. hucMSC derived exosomes promote functional recovery in spinal cord injury mice via attenuating inflammation. Materials Science and Engineering: C. 2018 Aug 1;89:194-204.

Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor EN, Timmers L, van Rijen HV, Doevendans PA, Pasterkamp G. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem cell research. 2013;10(3):301-12.

Bucan V, Vaslaitis D, Peck C-T, Strauß S, Vogt PM, Radtke C. Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury. Molecular Neurobiology. 2019 Mar 1;56(3):1812-24.

Zhou Z, Chen Y, Zhang H, Min S, Yu B, He B, and Jin A. Comparison of mesenchymal stromal cells from human bone marrow and adipose tissue for the treatment of spinal cord injury. Cytotherapy. (2013) 15: 434-48.




DOI: https://doi.org/10.22037/orlfps.v5i2.28004

Refbacks

  • There are currently no refbacks.


Creative Commons License
The Journal of Otorhinolaryngology and Facial Plastic Surgery is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.