A Novel Strategy for Spinal Cord Repair
December 1, 1997 3 minutes read
Source: Li Y, et al. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science 1997;277:2000-2003.
A number of recent papers have addressed two breaking areas of neuroscience research: first, neural precursors and adult neurogenesis, and second, new strategies for spinal cord repair. In a recent issue of Science, the first work at the interface of these fields was reported. Li et al reported that transplants of olfactory ensheathing cells into corticospinal tract lesions could promote both anatomic and functional reconstitution of corticospinal tract function. The olfactory ensheathing cell (OEC) is a peripheral glial cell described over the last decade, which supports the axons of the olfactory epithelium and joins those axons in entering the olfactory bulb. OECs have been described as functional hybrids and have a unique ability to traverse the PNS and CNS boundaries, remaining functional in each environment. Their role in supporting the recruitment of new neurons from progenitors in the olfactory epithelium, and supporting neuronal migration within the adult rodent olfactory subependyma, have highlighted their importance in directing both axonal extension and neuronal cell migration.
The authors postulated that OECs might provide a cellular substrate for axonal extension which would remain competent in the environment of the CNS (Schwann cells have largely failed to support axonal regrowth when implanted into adult brain and spinal cord). They lesioned the corticospinal tract of the adult rat and tested the postulate that OECs can support axonal regrowth across the lesion. They cultured OECs derived from adult rat olfactory nerves and bulbs for two weeks prior to implantation. Immediately after electrolytically lesioning the high cervical (C1- C2) cord unilaterally, the investigators injected homogenates of more than 105 cells (the percentage of these that were OECs was not determined) into the lesion sites. Most animals were sacrificed for histology from one to nine weeks thereafter; some were instead spared and tested behaviorally for evidence of functional regeneration at 2-3 months after lesioning and then sacrificed for histological correlation. Li et al found that: 1) OECs spread widely in the rostrocaudal plane and readily traversed the lesion gap; 2) they ensheathed and appeared to remyelinate regenerating axons; and 3) this process was associated with significant functional recovery of the affected forelimb. The authors did not report any non-OEC cell implant controls (e.g., CNS astrocytes or oligodendrocytes). As a result, they could not support the claim of OEC cells specifically mediating axonal regrowth, although past studies using Schwann cell grafts with a similar experimental design largely failed.
The authors did not report any quantitative data regarding the density or distribution of regenerated corticospinal efferents caudal to the lesion in their implanted experimental animals. Curiously, they did report some data for their lesioned, unimplanted controls, in whom as few as 1-2% of surviving corticospinal efferents were sufficient to permit their behavioral end point, forepaw reaching. Thus, a very minimal degree of anatomic regeneration might have profound functional significance in this system. Regardless of details, however, the clearly improved functional end point in this study informs us that another promising technique for functional regeneration of the injured spinal cord may soon be at hand. The past few years have witnessed the development of several alternative strategies for cord repair. These have included: 1) the surgical combination of fibrin bridges using aFGF addition, gray matter anastomoses, and peripheral nerve grafts (Science 1996; 273:510-513); 2) the active blockade of myelin-associated neurite inhibitors (Nature 1995;378:498-501); and 3) the application of neurotrophins active in ablated spinal tracts, such as NT-3 (Nature 1994;367:170-173). Li et al’s present study adds an intriguing new strategy to this potential toolbox. Unquestionably, the rational and synergistic combination of these diverse and largely non-overlapping approaches will permit hitherto unachieved degrees of anatomical and functional recovery after spinal cord injury. The strength, variety, and pace of these recent findings should offer hope that paralysis after spinal cord injury will become a fully treatable condition within our lifetimes. Steve Goldman, MD, PhD, Associate Professor of Neurology & Neuroscience, Associate Attending Neurologist, New York Hospital/Cornell Medical Center.
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