EXECUTIVE SUMMARY

Radial Glial Cells Promote Nerve Regeneration and Functional Recovery

Following Spinal Cord Injury

SUMMARY:  Dr. Martin Grumet in the Department of Cell Biology and Neuroscience at the W. M. Keck Center for Collaborative Neuroscience at Rutgers University has devised a method to prepare an enriched population of radial glial cells that have been shown in vivo to promote neuronal regeneration in a model of spinal cord injury.  Based upon this technology, it may now be possible to create such cells from human embryonic stem cells and apply them for the treatment of human CNS diseases and injury.

BACKGROUND:  Important advances have been made in understanding conditions that can influence survival and regrowth of neurons following injury to mature CNS tissue.  These advances include neurotrophic factors to promote survival and growth of neurons, embryonic neural tissues to provide cellular scaffolds to facilitate neuronal regrowth, and neutralization of inhibitors.  Another approach to repair neural damage is replacement of lost cells, in particular lost neurons and other cells.  The expanding possibilities to isolate and differentiate neural stem cells and neural restricted precursors have opened new opportunities for generating different types of neurons for replacement therapies.  These approaches are well suited for problems like Parkinson's disease where replacement of lost dopaminergic cells can yield significant recovery of function.  However, many other neurons, for example those that are damaged in spinal cord injury, have their cell bodies in locations (e.g. cerebral cortex) that are quite far from the site of injury in the spinal cord and therefore are difficult to replace.  Thus, there is a need for other strategies to protect neurons and promote their regrowth across sites of injury.

TECHNOLOGY:  Dr. Grumet has devised a method to prepare radial glial cells in a relatively stable form (as a cell line or clones).  This enriched population of radial glial cells is non-tumorigenic and capable of: exhibiting bipolar morphology, self-renewing, migrating and self-organizing in white matter, and supporting neuronal migration. 

Experimental evidence has shown that following spinal cord injury, the transplanted radial glial cells: 1) form bridges that span across the injury site and expand into spared spinal cord tissue; 2) suppress deposition of chondroitin sulfate proteoglycans (CSPGs), which are factors associated with neural damage; 3) suppress macrophage infiltration, which may mediate inflammatory processes and secrete CSPGs; 4) promote preservation and organization of neurofilaments in the spinal cord following injury; and 5) promote functional recovery.

PATENT STATUS:  PCT Patent Application WO2006047633 which claims this enriched population of radial glial cells was published on May 4, 2006 with priority to October 25, 2004.

PUBLICATIONS:  K. Hasegawa1, Y-W. Chang, H. Li, Y. Berlin, O. Ikeda, N. Kane-Goldsmith and M. Grumet, Embryonic Radial Glia Bridge Spinal Cord Lesions and Promote Functional Recovery Following Spinal Cord Injury, Experimental Neurology 193, 394– 410 (2004).