Mesenchymal Stem Cell Therapy for Apoptosis After Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a devastating clinical problem that has irreversible consequences, results in permanent functional loss, and life time disability (Sekhon and Fehlings, 2001). This debilitating condition often affects young and healthy individuals at the prime of their life, creates enormous physical and emotional cost, and places a significant financial burden to society at large (Ackery et al., 2004). Even though years of research have led to a better understanding in the pathophysiology of permanent neural injuries at the cellular level, much of the mechanism and processes of secondary injury at the molecular level remain to be elucidated. With modern molecular strategies and techniques, breakthroughs in the understanding of neuronal injury and neural regeneration provide new promises for reversal of spinal cord injury that once was thought to be permanent and irreversible (Carlson and Gorden, 2002). Spinal cord injury involves an initial mechanical or primary injury followed by a series of cellular and molecular secondary events that amplify the extent of the initial damage and results in the progressive destruction of spinal cord tissue. After acute contusion, the spinal cord undergoes a sequential progression of pathologic changes, including micro hemorrhage, cytotoxic edema, neuronal necrosis, axonal fragmentation, demyelination, further secondary cellular destruction and eventually cyst formation (Balentine, 1978; Balentine and Greene, 1984; Coutts and Keirstead, 2008). Damage to the spinal cord results in extensive proliferation of microglia and macrophages in and around the injury epicenter. This acute inflammatory response at the injury site is at least partly responsible for secondary spinal cord injury ( Popovich et al., 1997; Carlson et al., 1998; Taoka et al., 1998). The inflammatory cells (particularly macrophages/microglia) mediate tissue damage by producing a variety of cytotoxic factors including interleukins (Rice et al., 2007) and tumor necrosis factor-alpha (TNF-α) (Beattie et al., 2002). White matter breakdown begins at the grey-white matter junction with progressive edema (Dohrmann et al., 1972). Axoplasmic stasis and axonal swelling that contains multiple organelles, mitochondria, neurofilament, and smooth endoplasmic reticulum eventually undergo glandular dissolution and myelin