An Examination of the Mechanisms by which Neural Precursors Augment Recovery following Spinal Cord Injury: A Key Role for Remyelination

Abstract

The mechanisms by which neural precursor cells (NPCs) enhance functional recovery from spinal cord injury (SCI) remain unclear. Spinal cord injured rats were transplanted with wild-type mouse NPCs, shiverer NPCs unable to produce myelin, dead NPCs, or media. Most animals also received minocycline, cyclosporine, and perilesional infusion of trophins. Motor function was graded according to the BBB scale. H&E/LFB staining was used to assess gray and white matter, cyst, and lesional tissue. Mature oligodendrocytes and ED1 + inflammatory cells were quantitated. Confocal and electron microscopy were used to assess the relationship between the transplanted cells and axons. Pharmacotherapy and trophin infusion preserved gray matter, white matter, and oligodendrocytes. Trophin infusion also significantly increased cyst and lesional tissue volume as well as inflammatory infiltrate, and functional recovery was reduced. Animals transplanted with wild-type NPCs showed greatest functional recovery; animals transplanted with shiverer NPCs performed the worst. Wild-type NPCs remyelinated host axons. Shiverer NPCs ensheathed axons but did not produce MBP. These results suggest that remyelination by NPCs is an important contribution to functional recovery following SCI. Shiverer NPCs may prevent remyelination by endogenous cells capable of myelin formation. These findings suggest that remyelination is an important therapeutic target following SCI.

Transplantation of Induced Pluripotent Stem Cell-Derived Neural Stem Cells Mediate Functional Recovery Following Thoracic Spinal Cord Injury Through Remyelination of Axons

“…These data are supported by work done by our laboratory and others that has examined aNPCs isolated from wt-and shi-mice [34,42]. Yasuda et al [34] observed locomotor recovery following SCI with wt-aNPC transplantation but not shi-aNPC.…”

Transplantation of mature adipocyte-derived dedifferentiated fat cells promotes locomotor functional recovery by remyelination and glial scar reduction after spinal cord injury in mice

“…The transplanted cells also expressed markers of NPCs, neurons, and astrocytes, suggesting sustained multi-potency, and differentiated into neural cells in the injured environment, in accordance with other stem cells [1,2,4]. All of this directly supports Previous studies have demonstrated that remyelination after transplantation of NPCs contributes to functional recovery [6,15], as NPCs isolated from Shiverer mice -MBP null mice that do not form compact myelin -do not show the remyelination effect as NPCs from wild-type mice. In this study, promotion of remyelination contributed predominantly to functional recovery, more than glial scar reduction (Figs.…”

Self-assembling peptides optimize the post-traumatic milieu and synergistically enhance the effects of neural stem cell therapy after cervical spinal cord injury

“…Of particular interest are neural precursor cells (NPCs) which can differentiate into both neurons and glia [13]. NPCs have been shown to promote remyelination [14,15] and support functional recovery [16], making them very promising for the treatment of spinal cord injuries. Unfortunately, transplanted cells have poor survival rates.…”