Ensheathing glia transplants promote dorsal root regeneration and spinal reflex restitution after multiple lumbar rhizotomy

Abstract

Previously, we have shown that transplants of olfactory bulb ensheathing cells promoted regeneration of transected dorsal roots into the spinal cord. In this study, we assessed the ability of regenerating axons to make functional connections in the cord. Dorsal roots L3 to L6 were sectioned close to their entrance into the spinal cord and reapposed after injecting a suspension of ensheathing cells into each dorsal root entry zone (Group G). Afferent regeneration into the cord and recovery of spinal reflexes were compared with animals that received no injection (Group S) or culture medium without cells (Group C). Electrophysiological tests, to measure nerve conduction and spinal reflexes (H response and withdrawal reflex) evoked by stimulation of afferents of the sciatic nerve, were performed. At 14 days after surgery, H response was found in only 1 of 7 rats of Group G, and withdrawal reflexes were absent from all animals. At 60 days, the H response reappeared in 7 of 10 rats of Group G, and 1 of 5 of each of Groups C and S. The withdrawal reflex recovered in 4 of 10 rats of Group G, but in none of Groups C and S. Immunohistochemical labeling for CALCITONIN GENE– RELATED PEPTIDE (CGRP) in rats of Group G showed immunoreactive fibers entering the dorsal horn from sectioned roots, although at lower density than in the contralateral side. In conclusion, transplanted ensheathing cells promoted central regeneration and functional reconnection of regenerating sensory afferents. Ann Neurol 1999;45:207–215

Olfactory ensheathing cells transplanted in lesioned spinal cord prevent loss of spinal cord parenchyma and promote functional recovery

“…Transplants of cultured OECs mediate the reentry of regenerating dorsal root axons into the dorsal gray matter (Ramó n-Cueto and Nieto-Sampedro, 1994) and the synapses formed by these regenerating sensory fibers allowed functional restitution of spinal reflex arcs (Navarro et al, 1999;Taylor et al, 2001). When the corticospinal tract was focally lesioned, OECs transplanted into the lesion site enhanced the elongation of corticospinal axons inside of the transplanted area (Li et al, 1998).…”

Setting the stage for functional repair of spinal cord injuries: a cast of thousands

“…226 In this study, afferent ingrowth was reported to extend into the dorsal horn, in the areas of appropriate targets, and subsequent electrophysiological experiments suggested that these axons achieved functional reconnection. [227][228][229] However, recent data from our group and others indicate that OEC transplantation does not support regeneration of sensory axons across the injured DREZ. [230][231][232] Using OECs from the GFP mouse, we have observed that OEC injection into the spinal cord mechanically disrupts the DREZ, permitting sensory axon ingrowth but not functional regeneration involving the re-acquisition of appropriate targets on the other side of the injured DREZ.…”

Olfactory ensheathing cells: Historical perspective and therapeutic potential

“…OECs, tanycytes, and pituicytes all appear to make the CNS microenvironment more hospitable to growing axons, thus making them ideal candidates for glial cell transplantation into areas of CNS injury. Tanycytes (Prieto et al, 2000) and olfactory ensheathing cells (Ramon-Cueto and Nieto-Sampedro, 1994;Smale et al, 1996;Li et al, 1997Li et al, , 1998Navarro et al, 1999) have both been shown to promote the growth of CNS axons after grafting into the CNS of adult rats. Furthermore, all three putative Schwann cell-like macroglia possess the ability to myelinate DRG neurites in vitro (Gudino-Cabrera and Nieto-Sampedro, 2000).…”