Stem Cell Therapy for Spinal Cord Injury
Sicong Tu and Jian Tu
Introduction
Spinal cord injury remains a leading cause of long-term disability worldwide, resulting in enormous losses to individuals, families, and communities (WHO 2013a). World Health Organization has estimated that 500,000 people suffer a spinal cord injury each year. People with spinal cord injuries are two to five times more likely to die prematurely than people without a spinal cord injury (WHO 2013a). Up to 90 % of spinal cord injury cases are due to traumatic causes such as road traffic crashes, falls and violence (WHO 2013a). Symptoms of spinal cord injury may include partial or complete loss of sensory function or motor control of arms, legs, and/or body. The most severe spinal cord injury affects the systems that regulate bowel or bladder control, breathing, heart rate and blood pressure (WHO 2013b). Most people with spinal cord injury experience chronic pain, and an estimated 20-30 % show clinically significant signs of depression. People with spinal cord injury also risk developing secondary conditions that can be debilitating and even life-threatening, such as deep vein thrombosis, urinary tract infections, pressure ulcers and respiratory complications (WHO 2013a).
However, no effective therapy is available for treatment of individuals with spinal cord injury; nonetheless, researchers had tried some therapeutic agents like levodopa (Maric et al. 2008) and some neurotrophic factors in spinal cord injury (Cao and Dong 2013; Blesch et al. 2012; Boyce and Mendell 2014). This needs experimentation to confirm if these dopamine precursors and neurotrophic factors have any role in the treatment of spinal cord injury. Several other therapeutic agents like erythropoietin (Baptiste and Fehlings 2006), cannabinoid dexanabinol (McConeghy et al. 2012), and gamma-glutamylcysteine ethyl ester (Boyd-Kimball
S. Tu • J. Tu (*)
Prince of Wales Clinical School, University of New South Wales,
Sydney, NSW 2052, Australia
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P.V. Pham (ed.), Neurological Regeneration, Stem Cells in Clinical
Applications, DOI 10.1007/978-3-319-33720-3_8
et al. 2005) have all shown to have neuroprotective effect in human at experimental stage with remarkable improvement in post-traumatic spinal cord injury outcome.
Recent advancement in knowledge about stem cells promotes stem cells therapy in spinal cord injury. The stem cells may play an important role in the treatment of spinal cord injury by replacing damaged cells, and helping long-term functional recovery (Donnelly et al. 2012; Zhao et al. 2013; Davies et al. 2011). The search for stem cell therapy for human spinal cord injury is promising and progressing (Perrin et al. 2010). One obstacle in the search for an effective stem cell therapy is that the pathophysiology of spinal cord injury is largely unknown. This is because multiple cell types like neuronal cells, glial, and endothelial cells are usually involved in spinal cord injury. Furthermore, the vasculature of the spinal cord, especially the blood spinal cord barrier may be affected in spinal cord injury; this injury may be focal or diffuse axonal injury. This often results in neuronal mitochondrial dysfunction as we recently reported (Hu 2015). Taming these burgeoning effects of spinal cord injury requires neural stem cells that can differentiate into functional neurons and glial cells. We have reported that progenitor cells differentiated into neurons and glial in adult spinal cord, and an increase in astrocytic progeny forming reactive astrocytes to primarily limit cyst enlargement in posttraumatic syringomyelia (Tu et al. 2011, 2010).
This chapter is an optional extra to confirm whether we can achieve the translation of basic knowledge of neural stem cells into therapeutic options in persons with spinal cord injury by enhancing and integrating these neural precursor cells unto neurogenesis and directing these cells to the specified targets or through multipotency where the transplanted stem cells can differentiate into glial cells, neurons, and endothelial cells. As spinal cord injuries are not always focal but diffuse we need to induce these transplanted stem cells differentiating into appropriate phenotype for long-term structural and functional recovery. This chapter critically reviews current literature of others and our previous reports on neural stem cell research and proposing an approach for the quality clinical translation of stem cell research to therapy in spinal cord injury. The author explains the pathophysiology of spinal cord injury and proposes the “six-point schematic approach” to achieving quality bench to bedside translation of neural stem cells to therapy for spinal cord injury. The author also highlights the need for suitable clinical translation, coordination, and administration of research in the field of stem cell therapy for spinal cord injury.
