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Anti-inflammatory Mechanism of Bone Marrow Mesenchymal Stem Cell Transplantation in Rat Model of Spinal Cord Injury

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Abstract

To explore the effect of bone marrow mesenchymal stem cell (BMSC) transplantation on the levels of toll-like receptor 4 (TLR4), interleukin-1β (IL-1β), and tumor necrosis factor (TNF-α) in spinal cord tissue of rat model of spinal cord injury (SCI). BMSCs from 4-week-old male SD rats were isolated, cultured, and characterized after three generations using specific surface markers CD34 and CD44. Fifty four SD male rats were divided into sham group, model group, and cell transplantation group (18 rats each group). SCI model was generated using an improved Allen’s method. Rats in cell transplantation group were treated with BMSCs in caudal vein. Rats were sacrificed at 24 h, 72 h, and 7 d post-injury, and spinal cord tissues were taken out for detection of IL-1β and TNF-α tissue content by enzyme-linked immunosorbent assay. IL-1β and TNF-α mRNA expression was evaluated by qPCR and TLR4 protein expression was analyzed by Western blotting. IL-1β and TNF-α protein levels, as well as IL-1β, TNF-α mRNA, and TLR4 expression were significantly increased in rats with established SCI, and reached its peak in spinal cord tissues at 72 h after the initial injury (p < 0.01 comparing to sham group). BMSC transplantation resulted in significant decrease in IL-1β and TNF-α tissue content, as well as IL-1β, TNF-α mRNA, and TLR4 expression as compared with model group (p < 0.01). BMSCs may alleviate the damaging effect of spinal cord inflammation by weakening TLR4-mediated signaling pathways and reducing tissue content of IL-1β and TNF-α.

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References

  1. Devivo, M. J. (2012). Epidemiology of traumatic spinal cord injury: Trends and future implications. Spinal Cord, 50, 365–372.

    Article  CAS  PubMed  Google Scholar 

  2. Beattie, M. S., & Bresnahan, I. C. (2000). Cell death, repair, and recovery of function after spinal cord contusion injuries in rats. In R. C. Kalb & S. M. Strittmatter (Eds.), Neurobiology of spinal cord injury (pp. 1–21). Totowa, NJ: Humana Press.

    Chapter  Google Scholar 

  3. Tator, C. H. (1995). Update on the pathophysiology and pathology of acute spinal cord injury. Brain Pathology, 5, 407–413.

    Article  CAS  PubMed  Google Scholar 

  4. McDonald, J. W., & Sadowsky, C. (2002). Spinal-cord injury. Lancet, 359, 417–425.

    PubMed  Google Scholar 

  5. Rhoney, D. H., Luer, M. S., Hughes, M., & Hatt, J. (1996). New pharmacologic approaches to acute spinal cord injury. Pharmacotherapy., 16, 382–392.

    CAS  PubMed  Google Scholar 

  6. Young, W. (1987). Recovery mechanisms in spinal cord injury: Implications for regenerative therapy. In F. Seil (Ed.), Frontiers of clinical Neuroscience: Neural regeneration and transplantation (pp. 156–159). New York: Alan R Liss.

    Google Scholar 

  7. Yip, P. K., & Malaspina, A. (2012). Spinal cord trauma and the molecular point of no return. Molecular Neurodegeneration, 7, 6.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Anderson, D. K. (1993). Pathophysiology of spinal cord trauma. Annals of Emergency Medicine, 22, 987–992.

    Article  CAS  PubMed  Google Scholar 

  9. Geisler, F. H., Dorsey, F. C., & Coleman, W. P. (1991). Recovery of motor function after spinal-cord injury—a randomized, placebo-controlled trial with GM-1 ganglioside. New England Journal of Medicine, 324, 1829–1838.

    Article  CAS  PubMed  Google Scholar 

  10. Lapchak, P. A., Araujo, D. M., Song, D., et al. (2001). Neuroprotection by the selective cyclooxygenase-2 inhibitor SC-236 results in improvements in behavioral deficits induced by reversible spinal cord ischemia. Stroke, 32, 1220–1225.

    Article  CAS  PubMed  Google Scholar 

  11. Hausmann, O. N. (2003). Post-traumatic inflammation following spinal cord injury. Spinal Cord, 41, 369–378.

    Article  CAS  PubMed  Google Scholar 

  12. Oyinbo, C. A. (2011). Secondary injury mechanisms in traumatic spinal cord injury: A nugget of this multiply cascade. Acta Neurobiologiae Experimentalis (Wars), 71, 281–299.

    Google Scholar 

  13. Breslin, K., & Agrawal, D. (2012). The use of methylprednisolone in acute spinal cord injury: A review of the evidence, controversies, and recommendations. Pediatric Emergency Care, 28, 12388.

    Article  Google Scholar 

  14. Hawryluk, G. W., Rowland, J., Kwon, B. K., et al. (2008). Protection and repair of the injured spinal cord: A review of completed, ongoing, and planned clinical trials for acute spinal cord injury Neurosurg. Focus, 25, E14.

    Google Scholar 

  15. Cadotte, D. W., & Fehlings, M. G. (2011). Spinal cord injury: A systematic review of current treatment options. Clinical Orthopaedics and Related Research, 469, 7322–7327.

    Google Scholar 

  16. Kwon, B. K., Okon, E., Hillyer, J., et al. (2011). A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. Journal of Neurotrauma, 28, 1545.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Tator, C. H., Hashimoto, R., Raich, A., et al. (2012). Translational potential of preclinical trials of neuroprotection through pharmacotherapy for spinal cord injury. Journal of Neurosurgery: Spine, 17, 157–229.

    PubMed  Google Scholar 

  18. Lalu, M. M., McIntyre, L., Pugliese, C., et al. (2012). Safety of cell therapy with mesenchymal stromal cells (SafeCell): A systematic review and meta-analysis of clinical trials. PLoS One, 7, e47559.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Prockop, D. J., Brenner, M., Fibbe, W. E., et al. (2010). Defining the risks of mesenchymal stromal cell therapy. Cytotherapy, 12, 576–578.

    Article  PubMed  Google Scholar 

  20. Caplan, A. I. (2009). Why are MSCs therapeutic? New data: New insight. The Journal of Pathology, 217, 318–324.

    Article  CAS  PubMed  Google Scholar 

  21. Vawda, R., & Fehlings, M. G. (2013). Mesenchymal cells in the treatment of spinal cord injury: Current & future perspectives. Current Stem Cell Research & Therapy, 8, 25–38.

    Article  CAS  Google Scholar 

  22. Li, J., & Lepski, G. (2013). Cell transplantation for spinal cord injury: A systematic review. BioMed Research International, 2013, 786475.

    PubMed Central  PubMed  Google Scholar 

  23. Fleming, J. C., Norenberg, M. D., Ramsay, D. A., et al. (2006). The cellular inflammatory response in human spinal cords after injury. Brain, 129, 3249.

    Article  PubMed  Google Scholar 

  24. Nguyen, H. X., O’Barr, T. J., & Anderson, A. J. (2007). Polymorphonuclear leukocytes promote neurotoxicity through release of matrix metalloproteinases, reactive oxygen species, and TNF-alpha. Journal of Neurochemistry, 102, 900.

    Article  CAS  PubMed  Google Scholar 

  25. Uccelli, A., Benvenuto, F., Laroni, A., et al. (2011). Neuroprotective features of mesenchymal stem cells. Best Practice & Research Clinical Haematology, 24, 59–64.

    Article  CAS  Google Scholar 

  26. Neuhuber, B., Timothy Himes, B., Shumsky, J. S., et al. (2005). Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Research, 1035, 73–85.

    Article  CAS  PubMed  Google Scholar 

  27. Abrams, M. B., Dominguez, C., Pernold, K., et al. (2009). Multipotent mesenchymal stromal cells attenuate chronic inflammation and injury-induced sensitivity to mechanical stimuli in experimental spinal cord injury. Restorative Neurology and Neuroscience, 27, 307–321.

    PubMed  Google Scholar 

  28. Ohta, M., Suzuki, Y., Noda, T., et al. (2004). Bone marrow stromal cells infused into the cerebrospinal fluid promote functional recovery of the injured rat spinal cord with reduced cavity formation. Experimental Neurology, 187, 266–278.

    Article  CAS  PubMed  Google Scholar 

  29. Tran, C. T., Gargiulo, C., Thao, H. D., et al. (2011). Culture and differentiation of osteoblasts on coral scaffold from human bone marrow mesenchymal stem cells. Cell and Tissue Banking, 12(4), 247–261.

    Article  CAS  PubMed  Google Scholar 

  30. Sakata, N., Goto, M., Yoshimatsu, G., et al. (2011). Utility of co-transplanting mesenchymal stem cells in islet transplantation. World Journal of Gastroenterology, 17(47), 5150–5155.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Allen, A. R. (1911). Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column a preliminary report. JAMA, 57, 878–880.

    Google Scholar 

  32. David, S., & Kroner, A. (2011). Repertoire of microglial and macrophage responses after spinal cord injury. Nature Reviews Neuroscience, 12(7), 388–399.

    Article  CAS  PubMed  Google Scholar 

  33. van den Brand, R., Heutschi, J., Barraud, Q., et al. (2012). Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science, 336(6085), 1182–1185.

    Article  PubMed  Google Scholar 

  34. Zhang, N., Yin, Y., Xu, S. J., et al. (2012). Inflammation & apoptosis in spinal cord injury. Indian Journal of Medical Research, 35, 287–296.

    Google Scholar 

  35. David, S., & Kroner, A. (2011). Repertoire of microglial and macrophage responses after spinal cord injury. Nature Reviews Neuroscience, 12, 388–399.

    Article  CAS  PubMed  Google Scholar 

  36. Jaerve, A., & Muller, H. W. (2012). Chemokines in CNS injury and repair. Cell and Tissue Research, 349, 229–248.

    Article  CAS  PubMed  Google Scholar 

  37. Erşahin, M., Çevik, Ö., Akakın, D., et al. (2012). Montelukast inhibits caspase-3 activity and ameliorates oxidative damage in the spinal cord and urinary bladder of rats with spinal cord injury. Prostaglandins & Other Lipid Mediators, 99(3–4), 131–139.

    Article  Google Scholar 

  38. Bastien, D., & Lacroix, S. (2014). Cytokine pathways regulating glial and leukocyte function after spinal cord and peripheral nerve injury. Experimental Neurology, 258, 62–77.

    Article  CAS  PubMed  Google Scholar 

  39. Shi, Y., Zhang, D., Huff, T. B., et al. (2011). Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord. Journal of Biomedical Optics, 16(10), 106012-1–106012-4.

    Google Scholar 

  40. Liu, H., Peng, H., Wu, Y., et al. (2013). The promotion of bone regeneration by nanofibrous hydroxyapatite/chitosan scaffolds by effects on integrin-BMP/Smad signaling pathway in BMSCs. Biomaterials, 34(18), 4404–4417.

    Article  CAS  PubMed  Google Scholar 

  41. Blight, A. R., & Young, W. (1989). Central axons in injured cat spinal cord recover electrophysiological function following remyelination by Schwann cells. Journal of the Neurological Sciences, 91, 15–34.

    Article  CAS  PubMed  Google Scholar 

  42. Kayagaki, N., Wong, M. T., Stowe, I. B., et al. (2013). Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science, 341(6151), 1246–1249.

    Article  CAS  PubMed  Google Scholar 

  43. Caicco, M. J., Zahir, T., Mothe, A. J., et al. (2013). Characterization of hyaluronan-methylcellulose hydrogels for cell delivery to the injured spinal cord. Journal of Biomedical Materials Research Part A, 101A(5), 1472–1477.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Dongji Han & Yuke Tian

  2. Department of Pain Medicine, Wuhan Pu-Ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China

    Chenglong Wu, Qiuju Xiong & Ling Zhou

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  1. Dongji Han
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  2. Chenglong Wu
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  3. Qiuju Xiong
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  4. Ling Zhou
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Correspondence to Ling Zhou or Yuke Tian.

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Han, D., Wu, C., Xiong, Q. et al. Anti-inflammatory Mechanism of Bone Marrow Mesenchymal Stem Cell Transplantation in Rat Model of Spinal Cord Injury. Cell Biochem Biophys 71, 1341–1347 (2015). https://doi.org/10.1007/s12013-014-0354-1

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