Cell Therapy for CNS Trauma
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Cell therapy plays an important role in multidisciplinary management of the two major forms of central nervous system (CNS) injury, traumatic brain injury and spinal cord injury, which are caused by external physical trauma. Cell therapy for CNS disorders involves the use of cells of neural or non-neural origin to replace, repair, or enhance the function of the damaged nervous system and is usually achieved by transplantation of the cells, which are isolated and may be modified, e.g., by genetic engineering, when it may be referred to as gene therapy. Because the adult brain cells have a limited capacity to migrate to and regenerate at sites of injury, the use of embryonic stem cells that can be differentiated into various cell types as well as the use of neural stem cells has been explored. Preclinical studies and clinical trials are reviewed. Advantages as well as limitations are discussed. Cell therapy is promising for the treatment of CNS injury because it targets multiple mechanisms in a sustained manner. It can provide repair and regeneration of damaged tissues as well as prolonged release of neuroprotective and other therapeutic substances.
KeywordsCell therapy CNS trauma Embryonic stem cells Gene therapy Neural stem cells Neuroprotection Neuroregeneration Paraplegia Personalized medicine Spinal cord injury Transplantation of cells Traumatic brain injury
- 1.Jain, K. K. (2009). Cell therapy: Technologies, markets & companies. Basel, Switzerland: Jain PharmaBiotech Publications.Google Scholar
- 6.Watson, D. J., Longhi, L., Lee, E. B., et al. (2003). Genetically modified NT2 N human neuronal cells mediate long-term gene expression as CNS grafts in vivo and improve functional cognitive outcome following experimental traumatic brain injury. Journal of Neuropathology and Experimental Neurology, 62, 368–380.Google Scholar
- 7.Longhi, L., Watson, D. J., Saatman, K. E., et al. (2004). Ex vivo gene therapy using targeted engraftment of NGF expressing human NT2 N neurons attenuates cognitive deficits following traumatic brain injury in mice. Journal of Neurotrauma, 21, 1723–1736.Google Scholar
- 12.Tate, C. C., Shear, D. A., Tate, M. C., et al. (2009). Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain. Journal of Tissue Engineering and Regenerative Medicine. doi:10.1002/term.154.
- 15.Li, Y., Carlstedt, T., Berthold, C. H., & Raisman, G. (2004). Interaction of transplanted olfactory-ensheathing cells and host astrocytic processes provides a bridge for axons to regenerate across the dorsal root entry zone. Experimental Neurology, 188, 300–308. doi:10.1016/j.expneurol.2004.04.021.CrossRefGoogle Scholar
- 20.Davies, J. E., Huang, C., Proschel, C., et al. (2006). Astrocytes derived from glial-restricted precursors promote spinal cord repair. Journal of Biology (Online), 5, 7. doi:10.1186/jbiol35.
- 21.Ronsyn, M. W., Daans, J., Spaepen, G., et al. (2007). Plasmid-based genetic modification of human bone marrow-derived stromal cells: Analysis of cell survival and transgene expression after transplantation in rat spinal cord. BMC Biotechnology, 7, 90. doi:10.1186/1472-6750-7-90.CrossRefGoogle Scholar
- 22.Cummings, B. J., Uchida, N., Tamaki, S. J., et al. (2005). Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proceedings of the National Academy of Sciences of the United States of America, 102, 14069–14074. doi:10.1073/pnas.0507063102.CrossRefGoogle Scholar
- 27.Ziv, Y., Avidan, H., Pluchino, S., et al. (2006). Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury. Proceedings of the National Academy of Sciences of the United States of America, 103, 13174–13179. doi:10.1073/pnas.0603747103.CrossRefGoogle Scholar
- 28.Teng, Y. D., Lavik, E. B., Qu, X., et al. (2002). Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proceedings of the National Academy of Sciences of the United States of America, 99, 3024–3029. doi:10.1073/pnas.052678899.CrossRefGoogle Scholar
- 30.Lepore, A. C., Bakshi, A., Swanger, S. A., et al. (2005). Neural precursor cells can be delivered into the injured cervical spinal cord by intrathecal injection at the lumbar cord. Brain Research, 1045, 206–216.Google Scholar
- 31.Callera, F., & de Melo, C. (2007). Magnetic resonance tracking of magnetically labeled autologous bone marrow CD34+ cells transplanted into the spinal cord via lumbar puncture technique in patients with chronic spinal cord injury: CD34+ cells’ migration into the injured site. Stem Cells and Development, 16, 461–466. doi:10.1089/scd.2007.0083.CrossRefGoogle Scholar
- 32.Fujiwara, Y., Tanaka, N., Ishida, O., et al. (2004). Intravenously injected neural progenitor cells of transgenic rats can migrate to the injured spinal cord and differentiate into neurons, astrocytes and oligodendrocytes. Neuroscience Letters, 366, 287–291. doi:10.1016/j.neulet.2004.05.080.CrossRefGoogle Scholar
- 34.Park, H. C., Shim, Y. S., Ha, Y., et al. (2005). Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor. Tissue Engineering, 11, 913–922. doi:10.1089/ten.2005.11.913.CrossRefGoogle Scholar