Cellular transplantation strategies for spinal cord injury and translational neurobiology

Abstract

Summary: Basic science advances in spinal cord injury and regeneration research have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Among these interventions are cell-based approaches involving transplantation of neural and non-neural tissue elements that have potential for restoring damaged neural pathways or reconstructing intraspinal synaptic circuitries by either regeneration or neuronal/glial replacement. Notably, some of these strategies (e.g., grafts of peripheral nerve tissue, olfactory ensheathing glia, activated macrophages, marrow stromal cells, myelin-forming oligodendrocyte precursors or stem cells, and fetal spinal cord tissue) have already been translated to the clinical arena, whereas others have imminent likelihood of bench-to-bedside application. Although this progress has generated considerable enthusiasm about treating what once was thought to be a totally incurable condition, there are many issues to be considered relative to treatment safety and efficacy. The following review reflects on different experimental applications of intraspinal transplantation with consideration of the underlying pathological, pathophysiological, functional, and neuroplastic responses to spinal trauma that such treatments may target along with related issues of procedural and biological safety. The discussion then moves to an overview of ongoing and completed clinical trials to date. The pros and cons of these endeavors are considered, as well as what has been learned from them. Attention is primarily directed at preclinical animal modeling and the importance of patterning clinical trials, as much as possible, according to laboratory experiences.

Purification and in vitro characterization of adult canine olfactory ensheathing cells

“…The question of whether humOECs indeed share the in vitro and in vivo properties with rOECs cannot be definitely answered. Large animal models are generally considered the best testing ground to ensure that human trials can be ethically pursued (Kirk 2003;Reier 2004). Thus, studies on the canine system (Smith et al 2002;Jeffery et al 2005) not only have relevance for veterinary medicine, but may also serve as an intermediate step toward human therapy.…”

Recent therapeutic strategies for spinal cord injury treatment: possible role of stem cells

“…In a clinical trial in 2004, intravenous injection of autologous BMSCs resulted in a significant improvement, from American Spinal Injury Association score B to D, in only one over nine SCI patients [160]; however, BMSCs were well tolerated during the observation period. A phase I study established safety in acute complete SCI: of eight enrolled ASIA A patients, two improved to ASIA C after 6 months and three to ASIA C after 1 year, with some bladder recovery [97].…”

Genetic Manipulation of Neural Stem Cells for Transplantation into the Injured Spinal Cord

“…Depending on the severity of the injury, a cascade of events secondary to the primary injury further deteriorates adjacent tissues, including the eventual demyelination of spared neurons (Reier, 2004;Verma and Fawcett, 2005;Di Giovanni, 2006). The latter is clinically devastating because essential functions that are actually sustainable by spared neurons would be lost.…”