Since then, numerous experimental cell transplantation strategies have produced regeneration and partial recovery ( 2– 7). Pioneering work in cell therapy began in the late 1970s when Aguayo’s group showed that peripheral nerve grafts promoted regeneration of CNS axons ( 24) and Reier’s group showed that grafted fetal spinal cord supported regrowth of host axons ( 25). As discussed below, experimental cell transplantation strategies have generally been more effective in the subacute stage compared with the acute stage or the chronic stage, characterized by glial scarring and other inhibitory factors.Ĭell therapy is a promising strategy for SCI, and preclinical models demonstrate that cell transplantation can ameliorate some secondary events through neuroprotection and also restore lost tissue through regeneration. SCI is classified depending on the time elapsed from the initial injury: acute, within several days of SCI subacute, one to two weeks after injury or chronic, four weeks or more after injury. Some experimental rat models of SCI reproduce the typical pathology of human SCI, including the extradural compression, contusion, and crush models in rats ( 23). These and other cells secrete extracellular matrix and inhibitory molecules, such as chondroitin sulfate proteoglycans (CSPG), which compose the glial scar, resulting in a physical and chemical barrier to regeneration. In the subacute and chronic phases, a fluid-filled lentiform-shaped cavity or cyst forms in the center of the cord, with surrounding hypertrophic astrocytes and macrophages. Oligodendrocytes and neurons die, resulting in axonal demyelination and disruption of synaptic transmission. The primary and secondary injury mechanisms involve edema, hemorrhage, inflammation, apoptosis, necrosis, excitotoxicity, lipid peroxidation, electrolyte imbalance, ischemia/vasospasm, and blood vessel occlusion. The diagram shows a composite of pathophysiological events occurring after SCI, including the acute (e.g., edema and hemorrhage), subacute (e.g., inflammation), and chronic (e.g., cavitation) phases. However, neuroprotective agents alone may be insufficient to promote repair in major SCI where there is extensive tissue loss. Other neuroprotective agents with promising results in experimental animals are now being investigated in clinical SCI trials, including riluzole, a sodium channel blocker, and minocycline, an antiinflammatory agent ( 1, 18). Many SCI centers have stopped using steroids ( 17). Methylprednisolone demonstrated some neuroprotective effects in early experimental and clinical studies ( 15, 16), but its use is controversial because of limited efficacy and harmful side effects. Currently, there is limited pharmacotherapy for SCI patients. Acutely injured patients often require intensive care monitoring to treat cardiovascular instability and respiratory insufficiency. Acute treatment often involves surgical management, such as decompression, spinal stabilization, or realignment of displaced vertebrae ( 14) to prevent further injury from impingement on the spinal cord. The ASIA Impairment Scale (AIS) ranges from A to E, where A is a complete SCI and E denotes normal sensory and motor function. This review builds on several excellent previous reviews ( 2– 8) and discusses the incidence and pathophysiology of SCI as well as the key experimental and clinical stem cell strategies for SCI.Įpidemiology, etiology, incidence, and prevalence of SCIĪssessment of therapy in patients has improved markedly due to the development of the American Spinal Injury Association (ASIA) grading scale and quantitative scores of sensory and motor function now used worldwide to assess the severity of SCI and response to treatment ( 1). Stem cell therapy offers several highly attractive strategies for spinal cord repair, including replacement of damaged neuronal and glial cells, remyelination of spared axons, restoration of neuronal circuitry, bridging of lesion cavities, production of neurotrophic factors, antiinflammatory cytokines, and other molecules to promote tissue sparing and neovascularization, and a permissive environment for plasticity and axonal regeneration. Unfortunately, neurological recovery is limited, and most SCI patients still face substantial neurological dysfunction and lifelong disability. Current treatment includes surgery to decompress and stabilize the injury, prevention of secondary complications, management of any that do occur, and rehabilitation. Despite major advances in the medical and surgical care of SCI patients, no effective treatment exists for the neurological deficits of major SCI ( 1). Spinal cord injury (SCI) is a devastating condition, with sudden loss of sensory, motor, and autonomic function distal to the level of trauma.
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